# -*- coding: utf-8 -*-
"""
Generate: SKIN IMMUNOLOGY - 20-slide academic deck for Dermatology PGT-1
+ appendix: viva question bank + 1-minute revision sheet
"""
from pptx import Presentation
from pptx.util import Inches, Pt, Emu
from pptx.dml.color import RGBColor
from pptx.enum.text import PP_ALIGN, MSO_ANCHOR
from pptx.enum.shapes import MSO_SHAPE
import copy

prs = Presentation()
prs.slide_width = Inches(13.333)
prs.slide_height = Inches(7.5)
BLANK = prs.slide_layouts[6]
SW, SH = prs.slide_width, prs.slide_height

# ---------- palette ----------
NAVY   = RGBColor(0x0B, 0x2A, 0x4A)
ACCENT = RGBColor(0x1F, 0x6F, 0x8B)
GOLD   = RGBColor(0xB8, 0x86, 0x0B)
DARK   = RGBColor(0x22, 0x22, 0x22)
GREY   = RGBColor(0x5A, 0x5A, 0x5A)
WHITE  = RGBColor(0xFF, 0xFF, 0xFF)
BG     = RGBColor(0xFB, 0xFC, 0xFD)
BOX1   = RGBColor(0xE8, 0xF1, 0xF6)
BOX2   = RGBColor(0xDD, 0xEC, 0xE8)
BOX3   = RGBColor(0xF4, 0xE9, 0xD8)
BOX4   = RGBColor(0xEF, 0xE1, 0xEC)
BOX5   = RGBColor(0xE3, 0xE7, 0xF3)
ROWALT = RGBColor(0xF0, 0xF4, 0xF7)

def add_slide():
    s = prs.slides.add_slide(BLANK)
    s.background.fill.solid()
    s.background.fill.fore_color.rgb = BG
    return s

def txt(slide, left, top, width, height, text, size=16, color=DARK, bold=False,
        italic=False, align=PP_ALIGN.LEFT, font="Calibri", anchor=None, wrap=True):
    box = slide.shapes.add_textbox(Inches(left), Inches(top), Inches(width), Inches(height))
    tf = box.text_frame
    tf.word_wrap = wrap
    if anchor is not None:
        tf.vertical_anchor = anchor
    p = tf.paragraphs[0]
    p.text = text
    p.alignment = align
    p.font.size = Pt(size); p.font.bold = bold; p.font.italic = italic
    p.font.color.rgb = color; p.font.name = font
    return box

def header(slide, kicker, title, number):
    bar = slide.shapes.add_shape(MSO_SHAPE.RECTANGLE, 0, 0, SW, Inches(0.14))
    bar.fill.solid(); bar.fill.fore_color.rgb = ACCENT; bar.line.fill.background(); bar.shadow.inherit=False
    txt(slide, 0.55, 0.22, 8, 0.35, kicker.upper(), size=13, color=ACCENT, bold=True)
    txt(slide, 0.55, 0.52, 11.8, 0.65, title, size=27, color=NAVY, bold=True)
    ln = slide.shapes.add_shape(MSO_SHAPE.RECTANGLE, Inches(0.55), Inches(1.16), Inches(2.6), Pt(3))
    ln.fill.solid(); ln.fill.fore_color.rgb = GOLD; ln.line.fill.background(); ln.shadow.inherit=False
    txt(slide, 12.35, 0.22, 0.6, 0.35, str(number), size=13, color=GREY, align=PP_ALIGN.RIGHT)

def bullets(slide, items, left=0.65, top=1.4, width=12.0, height=5.55, size=17,
            title_color=NAVY, line_gap=6):
    box = slide.shapes.add_textbox(Inches(left), Inches(top), Inches(width), Inches(height))
    tf = box.text_frame; tf.word_wrap = True
    first = True
    for item in items:
        if isinstance(item, tuple):
            text, level = item[0], item[1]
            bold_head = item[2] if len(item) > 2 else None
        else:
            text, level, bold_head = item, 0, None
        p = tf.paragraphs[0] if first else tf.add_paragraph()
        first = False
        p.space_after = Pt(line_gap)
        p.level = 0
        marker = "●  " if level == 0 else ("–  " if level == 1 else "·  ")
        indent = 0.0 if level == 0 else (0.35 if level == 1 else 0.65)
        p.text = ""
        run = p.add_run(); run.text = " " * int(indent*4) + marker
        run.font.size = Pt(size); run.font.color.rgb = ACCENT if level == 0 else GREY
        run.font.bold = True
        run2 = p.add_run(); run2.text = text
        run2.font.size = Pt(size if level == 0 else size-1)
        run2.font.color.rgb = DARK
        run2.font.bold = bool(bold_head) if level == 0 and bold_head else False
    return box

def notes(slide, text):
    slide.notes_slide.notes_text_frame.text = text

def rounded_box(slide, left, top, width, height, text, fill=BOX1, tcolor=NAVY,
                 size=11, bold=True, line_color=None):
    shp = slide.shapes.add_shape(MSO_SHAPE.ROUNDED_RECTANGLE, Inches(left), Inches(top), Inches(width), Inches(height))
    shp.fill.solid(); shp.fill.fore_color.rgb = fill
    if line_color:
        shp.line.color.rgb = line_color; shp.line.width = Pt(1)
    else:
        shp.line.fill.background()
    shp.shadow.inherit = False
    tf = shp.text_frame; tf.word_wrap = True
    tf.margin_left = Pt(4); tf.margin_right = Pt(4); tf.margin_top = Pt(2); tf.margin_bottom = Pt(2)
    tf.vertical_anchor = MSO_ANCHOR.MIDDLE
    p = tf.paragraphs[0]; p.alignment = PP_ALIGN.CENTER
    p.text = text
    p.font.size = Pt(size); p.font.bold = bold; p.font.color.rgb = tcolor
    return shp

def arrow_label(slide, left, top, w=0.5, h=0.4, symbol="\u2192", color=ACCENT, size=20):
    txt(slide, left, top, w, h, symbol, size=size, color=color, bold=True, align=PP_ALIGN.CENTER)

def flow_row(slide, steps, top, left=0.55, total_width=12.2, box_h=0.85, size=11,
             colors=None, gap=0.42):
    n = len(steps)
    box_w = (total_width - gap*(n-1)) / n
    x = left
    for i, step in enumerate(steps):
        fill = colors[i % len(colors)] if colors else BOX1
        rounded_box(slide, x, top, box_w, box_h, step, fill=fill, size=size)
        if i < n-1:
            arrow_label(slide, x+box_w, top+box_h/2-0.22, gap, 0.4)
        x += box_w + gap
    return box_w

def table(slide, headers, rows, left=0.4, top=1.4, width=12.5, height=5.4,
          col_widths=None, header_size=13, body_size=11.5, header_fill=NAVY):
    n_rows = len(rows) + 1
    n_cols = len(headers)
    gshape = slide.shapes.add_table(n_rows, n_cols, Inches(left), Inches(top), Inches(width), Inches(height))
    tbl = gshape.table
    if col_widths:
        for i, w in enumerate(col_widths):
            tbl.columns[i].width = Inches(w)
    for j, htext in enumerate(headers):
        cell = tbl.cell(0, j)
        cell.text = htext
        cell.fill.solid(); cell.fill.fore_color.rgb = header_fill
        p = cell.text_frame.paragraphs[0]
        p.font.size = Pt(header_size); p.font.bold = True; p.font.color.rgb = WHITE
        p.alignment = PP_ALIGN.CENTER
        cell.vertical_anchor = MSO_ANCHOR.MIDDLE
    for i, row in enumerate(rows, start=1):
        for j, val in enumerate(row):
            cell = tbl.cell(i, j)
            cell.text = str(val)
            cell.fill.solid()
            cell.fill.fore_color.rgb = ROWALT if i % 2 == 0 else WHITE
            p = cell.text_frame.paragraphs[0]
            p.font.size = Pt(body_size); p.font.color.rgb = DARK
            p.alignment = PP_ALIGN.LEFT if j == 0 else PP_ALIGN.LEFT
            cell.vertical_anchor = MSO_ANCHOR.MIDDLE
            for para in cell.text_frame.paragraphs:
                para.font.size = Pt(body_size)
    return tbl

def footer(slide, text="Skin Immunology | Dermatology PGT-1 Seminar"):
    txt(slide, 0.55, 7.12, 9, 0.3, text, size=9, color=GREY)

# =====================================================================
# SLIDE 1 - TITLE
# =====================================================================
s = add_slide()
band = s.shapes.add_shape(MSO_SHAPE.RECTANGLE, 0, 0, SW, Inches(7.5))
band.fill.solid(); band.fill.fore_color.rgb = NAVY; band.line.fill.background(); band.shadow.inherit=False
band2 = s.shapes.add_shape(MSO_SHAPE.RECTANGLE, 0, Inches(4.6), SW, Inches(0.08))
band2.fill.solid(); band2.fill.fore_color.rgb = GOLD; band2.line.fill.background(); band2.shadow.inherit=False
txt(s, 1.0, 2.35, 11.3, 0.5, "DEPARTMENT OF DERMATOLOGY", size=18, color=RGBColor(0xB9,0xC9,0xDA), bold=True, align=PP_ALIGN.CENTER)
txt(s, 1.0, 2.85, 11.3, 1.3, "SKIN IMMUNOLOGY", size=54, color=WHITE, bold=True, align=PP_ALIGN.CENTER)
txt(s, 1.0, 3.95, 11.3, 0.5, "From Cutaneous Barrier to Clinical Dermatology", size=19, color=RGBColor(0xCF,0xDD,0xEA), italic=True, align=PP_ALIGN.CENTER)
txt(s, 1.0, 5.05, 11.3, 0.4, "Presenter: Dr. ______________  |  Dermatology PGT-1", size=17, color=WHITE, align=PP_ALIGN.CENTER)
txt(s, 1.0, 5.45, 11.3, 0.4, "Department of Dermatology, Venereology & Leprology", size=15, color=RGBColor(0xCF,0xDD,0xEA), align=PP_ALIGN.CENTER)
txt(s, 1.0, 5.8, 11.3, 0.4, "Institution: ______________________", size=15, color=RGBColor(0xCF,0xDD,0xEA), align=PP_ALIGN.CENTER)
txt(s, 1.0, 6.5, 11.3, 0.4, "Presented before HOD / Professors / Senior Residents / PG Trainees", size=13, color=GOLD, align=PP_ALIGN.CENTER, bold=True)
notes(s, "Good morning/afternoon Sir/Ma'am. Today I will present on Skin Immunology - the immunological "
          "framework that underlies almost every disease we see in dermatology OPD. My aim is to build a bridge "
          "from basic immunology to skin biology, to immunopathogenesis, and finally to clinical practice and "
          "current biologic therapeutics. I have used Bolognia's Dermatology and Rook's Textbook of Dermatology "
          "as the primary frameworks, supplemented by standard immunology texts and recent literature.")

# =====================================================================
# SLIDE 2
# =====================================================================
s = add_slide(); header(s, "Concept", "Why is Skin an Immune Organ?", 2)
bullets(s, [
    ("Physical barrier: stratum corneum + tight junctions + lipid lamellae limit pathogen entry", 0),
    ("Immunological barrier: keratinocytes, Langerhans cells, dermal DCs, T cells and mast cells are present at baseline, not only during disease", 0),
    ("Keratinocytes are active immune participants - they express PRRs, secrete cytokines/chemokines and AMPs (not just structural cells)", 0),
    ("Resident immune cell population: Langerhans cells, dermal dendritic cells, mast cells, macrophages, \u03b3\u03b4 T cells, TRM cells - the skin has more T cells than circulating blood (SALT - skin-associated lymphoid tissue)", 0),
    ("Both innate (immediate, non-specific) and adaptive (delayed, antigen-specific, memory-forming) arms operate together in skin", 0),
    ("Clinical importance: nearly every inflammatory, infective, autoimmune and neoplastic dermatosis has an immunological basis - understanding this drives rational diagnosis and targeted therapy", 0, True),
], size=16.5, height=4.35)
flow_row(s, ["BARRIER", "RECOGNITION\n(PRR-PAMP/DAMP)", "INNATE RESPONSE\n(AMPs, neutrophils, NK)", "ADAPTIVE RESPONSE\n(DC \u2192 T/B cells)", "RESOLUTION /\nMEMORY (TRM)"],
         top=5.95, colors=[BOX1,BOX2,BOX3,BOX4,BOX5], size=11, box_h=0.95)
footer(s)
notes(s, "Skin is the body's largest immune organ by surface area and cell number (SALT concept - "
      "skin-associated lymphoid tissue, Streilein). It performs three simultaneous jobs: physical exclusion, "
      "molecular sensing (PRRs sensing PAMPs/DAMPs), and generation of antigen-specific adaptive responses with "
      "durable memory (TRM cells). Keratinocytes are not bystanders - they are the first sensor and first "
      "responder. For a dermatologist this matters because psoriasis, atopic dermatitis, autoimmune bullous "
      "disease, drug reactions, leprosy and even acne are fundamentally immune-mediated processes playing out "
      "in this organ. Bolognia Ch. 'The Skin Immune System' frames this five-step conceptual flow: "
      "Barrier \u2192 Recognition \u2192 Innate response \u2192 Adaptive response \u2192 Resolution/Memory - which "
      "recurs throughout this talk.")

# =====================================================================
# SLIDE 3
# =====================================================================
s = add_slide(); header(s, "Framework", "Components of the Cutaneous Immune System", 3)
left_items = [
    ("1. Physical/chemical barrier - corneocytes, lipids, low pH, filaggrin", 0),
    ("2. Innate immune system - PRRs, complement, AMPs, neutrophils, NK cells", 0),
    ("3. Adaptive immune system - T cells, B cells, immunological memory (TRM)", 0),
    ("4. Resident immune cells - keratinocytes, LCs, dDCs, mast cells, macrophages", 0),
    ("5. Cytokines & chemokines - the signalling language between all cells", 0),
]
right_items = [
    ("6. Antimicrobial peptides - defensins, cathelicidin (LL-37), dermcidin", 0),
    ("7. Complement system - opsonisation, membrane attack, inflammation", 0),
    ("8. Neuroimmune interactions - sensory nerves, neuropeptides (SP, CGRP)", 0),
    ("9. Skin microbiome - commensals train and calibrate cutaneous immunity", 0),
]
bullets(s, left_items, left=0.65, top=1.45, width=6.0, height=4.0, size=15.5)
bullets(s, right_items, left=6.85, top=1.45, width=5.8, height=4.0, size=15.5)
txt(s, 0.65, 5.55, 11.7, 0.3, "High-yield concept: every dermatosis can be mapped onto a defect/exaggeration in one or more of these 9 components.", size=13.5, color=GOLD, bold=True, italic=True)
flow_row(s, ["Barrier", "Innate cells\n+ PRRs", "AMPs +\nComplement", "APCs\n(LC/dDC)", "T & B cells\n(adaptive)", "Cytokine\nnetwork"],
         top=6.0, colors=[BOX1,BOX2,BOX3,BOX4,BOX5,BOX1], size=10.5, box_h=0.9)
footer(s)
notes(s, "This is the master framework slide - Bolognia organizes cutaneous immunology under these nine "
      "pillars. Think of it as a checklist: barrier defects (filaggrin mutations) predispose to atopic "
      "dermatitis; AMP deficiency (LL-37) predisposes to infection but AMP excess drives psoriasis; microbiome "
      "dysbiosis (Staph aureus, Cutibacterium acnes, Malassezia) drives atopic dermatitis, acne and seborrhoeic "
      "dermatitis respectively. Neuroimmune crosstalk explains itch pathways (IL-31, substance P) which is why "
      "we now have neurokinin-1 antagonists in dermatology. Keeping this 9-point map in mind lets you answer "
      "almost any 'immunology of X disease' viva question systematically.")

# =====================================================================
# SLIDE 4
# =====================================================================
s = add_slide(); header(s, "Innate Barrier", "Epidermis as an Immune Barrier", 4)
bullets(s, [
    ("Keratinocytes are NOT passive structural cells - they are active immunological sentinels", 0, True),
    ("Physical layer: tight junctions (claudins) + stratum corneum + intercellular lipid lamellae (ceramides, cholesterol, free fatty acids) restrict pathogen and allergen penetration", 0),
    ("Filaggrin: aggregates keratin, maintains corneocyte integrity and skin pH; loss-of-function mutations \u2192 defective barrier \u2192 major genetic risk factor for atopic dermatitis and secondary allergic sensitisation", 0),
    ("Keratinocytes express pattern-recognition receptors (TLR1-6, 9; NOD1/2; inflammasome components) that sense microbial and danger signals", 0),
    ("On activation, keratinocytes secrete cytokines (IL-1\u03b1/\u03b2, TNF-\u03b1, TSLP, IL-33, IL-25 = epithelial \"alarmins\") and chemokines (CXCL9/10, CCL27) that recruit and instruct immune cells", 0),
    ("Keratinocytes produce antimicrobial peptides (\u03b2-defensins, LL-37) directly onto the skin surface", 0),
    ("Net concept: keratinocyte injury or barrier breach itself triggers an innate immune cascade, independent of true infection", 0, True),
], size=16, height=5.4)
footer(s)
notes(s, "This slide operationalises the exam favourite line: 'the keratinocyte is an immunocyte.' Barrier "
      "and immunity are inseparable in skin - a broken barrier (filaggrin mutation, mechanical trauma, soap "
      "surfactants) is itself a DAMP-generating event. TSLP, IL-33 and IL-25 are epithelial 'alarmins' released "
      "from stressed/damaged keratinocytes that directly activate dendritic cells, ILC2s and Th2 cells - central "
      "to the atopic march. This concept links directly to slide 16 (atopic dermatitis pathogenesis). Reference: "
      "Bolognia Dermatology, Section 1 'The Skin Immune System' and 'Structure and Function of the Skin.'")

# =====================================================================
# SLIDE 5
# =====================================================================
s = add_slide(); header(s, "Innate Arm", "Innate Immunity of Skin", 5)
bullets(s, [
    ("Pattern recognition receptors (PRRs) on keratinocytes, LCs, macrophages recognise PAMPs (microbial) and DAMPs (self, danger)", 0),
    ("Toll-like receptors (TLR2/6 - bacterial lipopeptides; TLR3 - viral dsRNA; TLR4 - LPS; TLR9 - CpG DNA/self-DNA complexes)", 0),
    ("NOD-like receptors and the inflammasome (NLRP3) \u2192 caspase-1 activation \u2192 cleave pro-IL-1\u03b2/pro-IL-18 to active forms", 0),
    ("Complement system - alternative pathway activation, opsonisation, C5a-driven chemotaxis (relevant in urticarial vasculitis, bullous disease)", 0),
    ("Effector cells: neutrophils (pustular psoriasis, Sweet syndrome), macrophages (granulomatous disease, leprosy), NK cells (viral surveillance, some drug reactions)", 0),
    ("Clinical hooks: NLRP3 mutations \u2192 cryopyrin-associated periodic syndromes (urticarial rash); TLR9-LL-37-DNA complexes \u2192 plasmacytoid DC activation in psoriasis", 0, True),
], size=15.5, height=4.1)
flow_row(s, ["Recognition\n(PRR binds PAMP/DAMP)", "Signalling\n(NF-\u03baB, inflammasome)", "Cytokine release\n(IL-1, TNF, type I IFN)", "Cell recruitment\n(neutrophils, monocytes)", "Pathogen\nelimination"],
         top=5.75, colors=[BOX1,BOX2,BOX3,BOX4,BOX5], size=10.5, box_h=0.95)
footer(s)
notes(s, "Frame this as a five-step logical sequence that faculty love to hear stated explicitly: Recognition "
      "\u2192 Signalling \u2192 Cytokine release \u2192 Recruitment \u2192 Elimination. Emphasise that innate immunity is "
      "fast (minutes-hours) and non-specific, buying time for adaptive immunity to develop. Clinically: TLR2 "
      "recognises Propionibacterium/Cutibacterium acnes and Mycobacterium leprae lipoproteins; NLRP3 "
      "inflammasome activation by UV, ATP and cholesterol crystals is implicated in photoaging and some "
      "autoinflammatory dermatoses. Reference: Bolognia, 'Innate Immunity'; Rook's, Ch. on cutaneous immunology.")

# =====================================================================
# SLIDE 6 - AMP TABLE
# =====================================================================
s = add_slide(); header(s, "Innate Effectors", "Antimicrobial Peptides (AMPs)", 6)
table(s, ["AMP", "Source", "Key Trigger", "Major Function", "Clinical Relevance"],
      [
        ["\u03b2-Defensins (hBD2, hBD3)", "Keratinocytes", "TLR activation, IL-17/IL-22, injury", "Broad antimicrobial; chemotactic for immune cells", "\u2191 in psoriasis (thick, less-infected plaques); \u2193 relative response in AD"],
        ["Cathelicidin (LL-37)", "Keratinocytes, neutrophils", "Vitamin D pathway, injury, TLR9", "Antimicrobial; forms complexes with self-DNA/RNA", "Activates pDCs via TLR9 \u2192 IFN-\u03b1 \u2192 drives psoriasis; \u2193 in AD (\u2191 infection risk); \u2191 in rosacea (vascular/inflammatory effects)"],
        ["Dermcidin", "Eccrine sweat glands", "Constitutive secretion in sweat", "Antimicrobial independent of injury/inflammation", "Reduced in atopic dermatitis sweat, contributing to S. aureus colonisation"],
        ["RNase 7", "Keratinocytes", "Cytokines, microbial contact", "Broad-spectrum antimicrobial (esp. antiviral)", "Contributes to baseline skin sterility despite constant exposure"],
      ],
      col_widths=[2.3,1.7,2.3,3.0,3.2], header_size=13, body_size=11.2)
txt(s, 0.4, 6.35, 12.5, 0.55, "Key clinical thread - LL-37: self-DNA/LL-37 complexes trigger TLR9 on plasmacytoid dendritic cells \u2192 type I interferon \u2192 myeloid DC activation \u2192 Th17 priming = an initiating event in psoriasis pathogenesis.", size=12.5, color=GOLD, bold=True, italic=True)
footer(s)
notes(s, "AMPs illustrate a unifying dermatology teaching point: too little AMP activity predisposes to "
      "infection (atopic dermatitis - low LL-37/defensins, recurrent S. aureus and eczema herpeticum), while "
      "too much/inappropriately activated AMP activity drives autoinflammation (psoriasis - LL-37-DNA complexes "
      "trigger TLR9 on plasmacytoid dendritic cells, an early event upstream of the IL-23/Th17 axis; Lande et al., "
      "Nature 2007, is the key paper). Rosacea shows abnormal cathelicidin processing (elevated serine protease "
      "activity/kallikrein-5) producing pro-inflammatory LL-37 fragments. Acne involves innate activation by "
      "C. acnes via TLR2. Mention this LL-37-psoriasis link explicitly - it is a favourite viva question.")

# =====================================================================
# SLIDE 7
# =====================================================================
s = add_slide(); header(s, "Antigen Presentation", "Dendritic Cells and Antigen Presentation", 7)
bullets(s, [
    ("Langerhans cells (LC): reside in the epidermis (suprabasal), extend dendrites between keratinocytes via tight-junction proteins to sample antigen without breaching the barrier", 0),
    ("Dermal dendritic cells (dDC): reside in the dermis; subsets include CD1a+ dDCs and CD14+ dDCs with distinct T-cell polarising abilities", 0),
    ("Both capture antigen \u2192 process it \u2192 load peptides onto MHC II (exogenous antigen, for CD4+ T cells) or cross-present on MHC I (for CD8+ T cells)", 0),
    ("On activation, DCs upregulate CCR7, migrate via afferent lymphatics to draining lymph nodes", 0),
    ("In the lymph node, DCs present antigen to naive T cells with co-stimulation (CD80/86-CD28) \u2192 T-cell priming and polarisation", 0),
], size=16, height=3.6)
flow_row(s, ["Antigen\ncapture (skin)", "Processing +\nMHC loading", "Maturation\n(CCR7 up)", "Migration to\nlymph node", "Presentation to\nnaive T cell", "T-cell priming\n& polarisation"],
         top=5.1, colors=[BOX1,BOX2,BOX3,BOX4,BOX5,BOX1], size=10, box_h=0.95)
txt(s, 0.65, 6.25, 11.9, 0.9, "Clinical correlation: Langerhans cells are the key sensitising APC in allergic contact dermatitis "
    "(hapten capture \u2192 lymph node priming) and central to cutaneous immune surveillance against early cutaneous malignancy/infection.", size=13.5, color=GOLD, italic=True, bold=True)
footer(s)
notes(s, "Distinguish LC (epidermal, Langerin/CD207+, self-renewing from embryonic precursors, radio-resistant) "
      "from dermal DCs (dermis, more heterogeneous, replenished from blood monocytes/precursors). Functionally, "
      "LCs were classically considered pro-inflammatory sensitisers in contact dermatitis, but current data shows "
      "they can also promote tolerance in some contexts - a nuance faculty may probe. dDCs are important sources "
      "of IL-23/IL-12 driving Th17/Th1 responses in psoriasis. The antigen capture \u2192 migration \u2192 presentation "
      "\u2192 priming sequence is the bridge from innate sensing to adaptive, antigen-specific immunity. Reference: "
      "Bolognia 'The Skin Immune System', Rook's Ch. on Langerhans cells and dendritic cells.")

# =====================================================================
# SLIDE 8
# =====================================================================
s = add_slide(); header(s, "Adaptive Arm", "T Cells in Skin", 8)
bullets(s, [
    ("T-cell subsets present in skin: CD4+ helper, CD8+ cytotoxic, regulatory T cells (Treg), and tissue-resident memory T cells (TRM)", 0),
    ("Skin homing: naive T cells primed in lymph node acquire cutaneous lymphocyte-associated antigen (CLA) + chemokine receptors (CCR4, CCR10) \u2192 bind E-selectin/CCL17/CCL27 on dermal venules \u2192 enter skin", 0),
    ("TRM cells remain in skin long-term without recirculating \u2192 rapid local recall response \u2192 explain fixed-site recurrence (e.g., fixed drug eruption, herpes recurrence, psoriasis plaque recurrence at same site)", 0, True),
], size=15.5, height=2.1, top=1.35)
table(s, ["Subset","Signature cytokine(s)","Main function","Key dermatoses"],
      [
        ["Th1","IFN-\u03b3, TNF-\u03b1","Macrophage activation, intracellular pathogen clearance","Tuberculoid leprosy, lichen planus, vitiligo"],
        ["Th2","IL-4, IL-5, IL-13","B-cell/IgE help, eosinophil recruitment","Atopic dermatitis, allergic disease"],
        ["Th17","IL-17A/F, IL-22","Neutrophil recruitment, AMP induction","Psoriasis, psoriatic arthritis"],
        ["Th22","IL-22","Keratinocyte proliferation, barrier genes","Psoriasis (co-driver), AD (co-driver)"],
        ["Treg","IL-10, TGF-\u03b2 (FOXP3+)","Peripheral tolerance, suppression","Loss \u2192 autoimmunity; deficient in AD/psoriasis lesions"],
        ["CD8+ CTL","IFN-\u03b3, perforin, granzyme","Cytotoxicity vs. infected/self keratinocytes","Lichen planus, vitiligo, GVHD, SJS/TEN, lepromatous reactions"],
      ], top=3.6, height=3.35, col_widths=[1.3,2.6,3.7,4.6], header_size=13, body_size=11)
footer(s)
notes(s, "CLA (cutaneous lymphocyte-associated antigen) is a carbohydrate modification of PSGL-1 that binds "
      "E-selectin on inflamed dermal endothelium - this is the classic viva definition. TRM cells (CD69+, CD103+) "
      "are the mechanistic explanation for why psoriasis and fixed drug eruptions recur at exactly the same skin "
      "site after apparent clearance - a genuinely high-yield modern concept (Clark lab data). The Th-subset table "
      "is the single most examined table in cutaneous immunology - be fluent in cytokine \u2192 disease mapping in "
      "both directions. SJS/TEN is CD8+ cytotoxic T-cell/NK mediated via granulysin and Fas-FasL.")

# =====================================================================
# SLIDE 9 - Th polarization
# =====================================================================
s = add_slide(); header(s, "Adaptive Arm", "T-Helper Cell Polarisation", 9)
rounded_box(s, 5.1, 1.5, 3.1, 0.7, "NAIVE CD4+ T CELL", fill=NAVY, tcolor=WHITE, size=15)
for i,(x) in enumerate([0.5,2.9,5.3,7.7,10.1]):
    arrow_label(s, x+1.0, 2.25, 0.35, 0.35, "\u2193", size=16)
cols = [
    ("Th1", "IL-12, IFN-\u03b3", "T-bet", "IFN-\u03b3, TNF-\u03b1", "Vitiligo, tuberculoid leprosy, lichen planus", BOX1),
    ("Th2", "IL-4", "GATA-3", "IL-4, IL-5, IL-13", "Atopic dermatitis, allergic conditions", BOX2),
    ("Th17", "IL-6, IL-23, TGF-\u03b2", "ROR\u03b3t", "IL-17A/F, IL-22", "Psoriasis, psoriatic arthritis", BOX3),
    ("Th22", "IL-6, TNF-\u03b1", "AHR", "IL-22", "Psoriasis (co-driver), AD (co-driver)", BOX4),
    ("Treg", "TGF-\u03b2, IL-2", "FOXP3", "IL-10, TGF-\u03b2", "Deficiency \u2192 autoimmunity/atopy", BOX5),
]
x = 0.5
w = 2.4
for name, diffcyto, tf_, sigcyto, disease, color in cols:
    rounded_box(s, x, 2.65, w, 0.55, name, fill=color, tcolor=NAVY, size=15)
    txt(s, x, 3.25, w, 1.7,
        "Induced by: " + diffcyto + "\n\nTF: " + tf_ + "\n\nSecretes: " + sigcyto,
        size=10.5, color=DARK)
    b = s.shapes.add_shape(MSO_SHAPE.ROUNDED_RECTANGLE, Inches(x), Inches(5.15), Inches(w), Inches(1.55))
    b.fill.solid(); b.fill.fore_color.rgb = WHITE; b.line.color.rgb = color; b.line.width = Pt(1.25); b.shadow.inherit=False
    tf2 = b.text_frame; tf2.word_wrap = True; tf2.vertical_anchor = MSO_ANCHOR.MIDDLE
    tf2.margin_left=Pt(4); tf2.margin_right=Pt(4)
    p = tf2.paragraphs[0]; p.alignment = PP_ALIGN.CENTER
    p.text = disease; p.font.size = Pt(10.5); p.font.bold = True; p.font.color.rgb = NAVY
    x += w + 0.13
footer(s)
notes(s, "This is the master differentiation slide - be able to draw it from memory. Naive CD4+ T cells "
      "polarise depending on the local cytokine milieu set up by innate cells/keratinocytes: IL-12 \u2192 Th1 "
      "(T-bet); IL-4 \u2192 Th2 (GATA-3); IL-6+IL-23+TGF-\u03b2 \u2192 Th17 (ROR\u03b3t), maintained/expanded by IL-23; "
      "AHR-driven signals \u2192 Th22; TGF-\u03b2+IL-2 (without inflammatory cytokines) \u2192 Treg (FOXP3). "
      "IL-23 does not initiate Th17 differentiation but is essential for Th17 survival, expansion and "
      "pathogenic function - this nuance is commonly tested. Each axis maps to a therapeutic target discussed "
      "in slide 18 (e.g., anti-IL-23, anti-IL-17, anti-IL-4R\u03b1, JAK inhibitors affecting multiple axes downstream).")

# =====================================================================
# SLIDE 10 - Cytokine table
# =====================================================================
s = add_slide(); header(s, "Signalling", "Cytokines and Chemokines in Dermatology", 10)
table(s, ["Cytokine","Source","Major Action","Dermatological Relevance","Targeted Therapy"],
      [
        ["TNF-\u03b1","Macrophages, DCs, T cells","Pro-inflammatory, endothelial activation","Psoriasis, HS, pyoderma gangrenosum","Adalimumab, infliximab, etanercept"],
        ["IL-23","Dermal DCs, macrophages","Maintains/expands Th17","Psoriasis, PsA","Ustekinumab (p40), guselkumab/risankizumab (p19)"],
        ["IL-17A/F","Th17, \u03b3\u03b4T, ILC3","Neutrophil recruitment, keratinocyte activation","Psoriasis","Secukinumab, ixekizumab, bimekizumab"],
        ["IL-4 / IL-13","Th2, ILC2, mast cells","IgE class switching, barrier suppression","Atopic dermatitis, allergy","Dupilumab (IL-4R\u03b1), tralokinumab (IL-13)"],
        ["IL-31","Th2 cells","Direct pruritogen via sensory neurons","Atopic dermatitis, prurigo nodularis","Nemolizumab"],
        ["IL-5","Th2 cells","Eosinophil maturation/survival","Eosinophilic dermatoses","Mepolizumab"],
        ["IL-1/IL-1\u03b2","Keratinocytes, macrophages","Inflammasome output, fever, acute inflammation","Acne, autoinflammatory syndromes","Anakinra, canakinumab"],
        ["IFN-\u03b3","Th1, CD8+, NK cells","Macrophage activation","Vitiligo, lichen planus, GVHD","JAK1/2 inhibitors (indirect)"],
        ["TGF-\u03b2","Treg, keratinocytes","Immunosuppression, fibrosis","Scleroderma/fibrosis, wound healing","-"],
      ], top=1.4, height=5.55, col_widths=[1.5,2.1,3.1,3.0,2.8], header_size=12.5, body_size=10.3)
footer(s)
notes(s, "This slide is the conceptual pivot of the entire talk: cytokines are the shared language linking "
      "immunopathogenesis to modern targeted therapeutics. Group cytokines into functional families: TNF-\u03b1 "
      "(broad pro-inflammatory, oldest biologic target), IL-23/IL-17 axis (psoriasis), IL-4/IL-13/IL-31 (Th2/atopic "
      "axis), IL-1 family (innate/autoinflammatory), IFN-\u03b3 (Th1/cytotoxic diseases). When asked 'why does drug X "
      "work in disease Y', trace back through this table to the pathway. Note IL-23 inhibitors spare IL-12 (only "
      "block p19), reducing effects on Th1/anti-mycobacterial immunity compared with older anti-p40 agents like "
      "ustekinumab.")

# =====================================================================
# SLIDE 11 - cell network
# =====================================================================
s = add_slide(); header(s, "Integration", "Skin Immune Cell Network", 11)
center = rounded_box(s, 5.35, 3.35, 2.6, 0.9, "KERATINOCYTE\n(central hub)", fill=NAVY, tcolor=WHITE, size=13)
outer = [
    ("Langerhans cell\n(antigen capture)", 0.55, 1.4, BOX1),
    ("Dermal DC\n(IL-23/IL-12 source)", 5.35, 1.4, BOX2),
    ("Mast cell\n(histamine, IL-31 axis)", 10.1, 1.4, BOX3),
    ("Macrophage\n(phagocytosis, granuloma)", 0.55, 5.6, BOX4),
    ("T cell (Th1/2/17/22/Treg,\nTRM, CD8+)", 5.35, 5.6, BOX5),
    ("B cell / Plasma cell\n(antibody production)", 10.1, 5.6, BOX1),
]
for text, x, y, color in outer:
    rounded_box(s, x, y, 2.7, 0.9, text, fill=color, size=11.5)
# connecting lines
from pptx.enum.shapes import MSO_CONNECTOR
def connect(x1,y1,x2,y2):
    conn = s.shapes.add_connector(MSO_CONNECTOR.STRAIGHT, Inches(x1), Inches(y1), Inches(x2), Inches(y2))
    conn.line.color.rgb = ACCENT; conn.line.width = Pt(1.25)
connect(1.9,2.3,6.0,3.5); connect(6.6,2.3,6.6,3.35); connect(11.45,2.3,7.2,3.6)
connect(1.9,5.6,6.0,4.3); connect(6.7,5.6,6.7,4.25); connect(11.45,5.6,7.4,4.1)
txt(s, 0.55, 6.75, 11.9, 0.5, "Keratinocytes both respond to and instruct every resident immune cell - true bidirectional cross-talk, not a one-way cascade.", size=13, color=GOLD, bold=True, italic=True)
notes(s, "Use this slide to narrate cross-talk rather than reading it: keratinocytes release alarmins/AMPs that "
      "activate LCs, dDCs, mast cells and macrophages; dDCs produce IL-23/IL-12 to polarise T cells; T cells "
      "release IL-17/IL-22/IFN-\u03b3/IL-4 that act back on keratinocytes, closing the loop and amplifying disease "
      "(e.g., the psoriasis 'vicious cycle' between keratinocytes and Th17 cells). Mast cells bridge innate and "
      "adaptive responses in urticaria/atopic disease. B cells/plasma cells contribute antibody-mediated disease "
      "(pemphigus, bullous pemphigoid) discussed in slide 13. This integrated view is what faculty expect you to "
      "reproduce verbally, even without the diagram.")

# =====================================================================
# SLIDE 12 - trafficking
# =====================================================================
s = add_slide(); header(s, "Trafficking", "Cutaneous Immune Surveillance and Trafficking", 12)
bullets(s, [
    ("Skin-homing memory T cells express cutaneous lymphocyte-associated antigen (CLA), a carbohydrate ligand for E-selectin", 0),
    ("Chemokine receptor-ligand pairs direct organ-specific homing: CCR4-CCL17(TARC), CCR10-CCL27(CTACK) for skin homing; CXCR3-CXCL9/10/11 for Th1/CD8 recruitment into inflamed skin", 0),
    ("Sequence of extravasation: selectin-mediated rolling \u2192 chemokine-triggered integrin activation \u2192 firm adhesion (LFA-1/ICAM-1) \u2192 diapedesis \u2192 chemotactic migration into dermis/epidermis", 0),
], size=15.5, top=1.35, height=2.4)
flow_row(s, ["Rolling\n(selectins, CLA)", "Activation\n(chemokines)", "Firm adhesion\n(LFA-1-ICAM-1)", "Diapedesis\n(transmigration)", "Chemotaxis /\ntissue localisation"],
         top=3.9, colors=[BOX1,BOX2,BOX3,BOX4,BOX5], size=11, box_h=0.95)
txt(s, 0.65, 5.15, 11.9, 1.6,
    "Clinical connections: elevated serum CCL17/TARC correlates with atopic dermatitis severity; CXCL9/10 (IFN-\u03b3 "
    "induced) recruit cytotoxic lymphocytes in vitiligo and lichen planus; alefacept (historic) and efalizumab "
    "targeted LFA-1/CD2 adhesion pathways in psoriasis. Understanding this cascade explains why blocking a single "
    "adhesion/chemokine step can abort an entire inflammatory dermatosis.", size=14, color=DARK)
footer(s)
notes(s, "This is the mechanistic explanation for how circulating, antigen-primed T cells find their way "
      "specifically back to skin rather than gut or lung - the organ-specific homing concept (Butcher's "
      "'multistep paradigm', adapted to skin by Michael Girardi/Clark). Emphasise CLA and CCR4-CCL17 as the two "
      "highest yield molecules. CXCL9/10-CXCR3 is particularly important in interferon-driven diseases (vitiligo, "
      "lichen planus, dermatomyositis) and is now a JAK-inhibitor-relevant pathway since JAK1/2 inhibition blocks "
      "IFN-\u03b3-CXCL9/10 signalling - explaining efficacy of ruxolitinib/tofacitinib in vitiligo repigmentation.")

# =====================================================================
# SLIDE 13
# =====================================================================
s = add_slide(); header(s, "Adaptive Arm", "Humoral Immunity: B Cells and Antibodies", 13)
bullets(s, [
    ("B cells recognise antigen via BCR, receive T-cell help (Th2/Tfh), undergo class switching \u2192 differentiate into antibody-secreting plasma cells", 0),
    ("Immunoglobulin classes in skin disease: IgG (pemphigus, bullous pemphigoid, lupus), IgA (dermatitis herpetiformis, linear IgA disease), IgE (atopic disease, urticaria), IgM (early/acute immune complex disease)", 0),
    ("Autoantibodies directly cause disease by binding structural skin proteins \u2192 loss of cell adhesion or complement/Fc-receptor-mediated tissue injury", 0, True),
], size=16, top=1.35, height=2.3)
table(s, ["Disease","Target Antigen","Antibody","Mechanism of Damage"],
      [
        ["Pemphigus vulgaris/foliaceus","Desmoglein 3 / Desmoglein 1","IgG4/IgG1","Steric hindrance + signalling \u2192 loss of keratinocyte adhesion (acantholysis)"],
        ["Bullous pemphigoid","BP180 (COL17A1), BP230","IgG (+ IgE)","Complement activation, Fc-receptor-mediated neutrophil/eosinophil recruitment at BMZ"],
        ["Dermatitis herpetiformis","Epidermal transglutaminase","IgA","Granular IgA deposits at dermal papillae, neutrophil recruitment"],
        ["Chronic spontaneous urticaria","IgE receptor (FcεRI) / IgE itself","IgG (autoimmune subtype)","Mast cell activation via autoantibody or IgE cross-linking"],
      ], top=3.9, height=2.9, col_widths=[3.0,2.9,2.0,4.6], header_size=12.5, body_size=10.8)
footer(s)
notes(s, "Key teaching point for viva: pemphigus antibodies bind desmosomal cadherins directly disrupting "
      "cell-cell adhesion (largely complement-independent, direct steric/signalling effect - p38 MAPK pathway), "
      "producing intraepidermal blisters; bullous pemphigoid antibodies bind hemidesmosomal BP180/BP230 at the "
      "basement membrane zone and act mainly via complement activation and Fc-receptor-mediated inflammatory "
      "cell recruitment, producing subepidermal blisters. This mechanistic difference explains why pemphigus "
      "blisters are flaccid/intraepidermal (Nikolsky positive) while BP blisters are tense/subepidermal. "
      "Reference: Bolognia, Chapters on Pemphigus and Pemphigoid.")

# =====================================================================
# SLIDE 14 - tolerance
# =====================================================================
s = add_slide(); header(s, "Autoimmunity", "Immunological Tolerance and Autoimmunity", 14)
bullets(s, [
    ("Central tolerance: autoreactive T/B cell clones deleted or edited during development (thymus/bone marrow)", 0),
    ("Peripheral tolerance: anergy (signal 1 without co-stimulation), Treg-mediated suppression, immune checkpoints (CTLA-4, PD-1/PD-L1), and regulated apoptosis of autoreactive cells", 0),
    ("Breakdown mechanisms: molecular mimicry, epitope spreading, defective Treg number/function, checkpoint dysregulation (e.g., checkpoint-inhibitor drugs unmasking autoimmunity), aberrant antigen exposure after tissue damage", 0),
], size=15.5, top=1.35, height=2.5)
flow_row(s, ["Normal tolerance\n(central + peripheral)", "Breakdown\n(Treg loss, mimicry,\ncheckpoint failure)", "Autoreactive T/B\ncell activation", "Autoantibody /\nautoreactive T-cell", "Tissue damage\n(clinical disease)"],
         top=4.0, colors=[BOX5,BOX3,BOX2,BOX1,BOX4], size=10.5, box_h=1.0)
txt(s, 0.65, 5.35, 11.9, 1.4,
    "Dermatological examples: Pemphigus vulgaris (anti-desmoglein 3), Bullous pemphigoid (anti-BP180), Cutaneous "
    "lupus (anti-Ro/La, immune complex + interferon-driven), Dermatomyositis (anti-Mi-2/MDA5/TIF1-\u03b3, type I "
    "IFN signature), Vitiligo (CD8+ cytotoxic T cells destroy melanocytes, loss of Treg control).", size=14, color=DARK)
footer(s)
notes(s, "Anchor concept: autoimmunity = loss of self-tolerance with subsequent tissue-specific damage. Bring in "
      "checkpoint inhibitor-induced dermatological adverse events (vitiligo-like depigmentation, lichenoid "
      "eruptions, bullous pemphigoid) as a topical, high-yield modern example connecting immune checkpoints to "
      "real clinical practice - a favourite current-affairs question. Vitiligo is increasingly viewed as an "
      "autoimmune/autoinflammatory disease with CD8+ T cells producing IFN-\u03b3 that signals through keratinocyte "
      "CXCR3 ligands, recruiting more CTLs - hence JAK inhibitor efficacy.")

# =====================================================================
# SLIDE 15 - hypersensitivity
# =====================================================================
s = add_slide(); header(s, "Classification", "Hypersensitivity Reactions in Dermatology", 15)
table(s, ["Type","Mechanism","Key Mediators","Dermatological Examples"],
      [
        ["I","IgE-mediated mast cell degranulation","Histamine, tryptase, leukotrienes","Urticaria, angioedema, atopic dermatitis flares, anaphylaxis"],
        ["II","Antibody directed against cell/tissue antigen","IgG/IgM + complement","Pemphigus, bullous pemphigoid, some drug-induced cytopenias"],
        ["III","Immune complex deposition","Complement, immune complexes","Cutaneous small-vessel vasculitis, serum sickness, urticarial vasculitis"],
        ["IV","T-cell mediated (delayed-type)","T cells (see subtypes below)","Allergic contact dermatitis, morbilliform drug eruption, TB/leprosy reactions, SJS/TEN"],
      ], top=1.4, height=2.9, col_widths=[0.9,3.4,2.9,5.3], header_size=13, body_size=11.5)
table(s, ["Type IV subtype","Cells / Cytokines","Clinical example"],
      [
        ["IVa","Th1, IFN-\u03b3, macrophage activation","Tuberculin reaction, allergic contact dermatitis (early)"],
        ["IVb","Th2, IL-4/5/13, eosinophils","Maculopapular drug eruption with eosinophilia (DRESS-spectrum)"],
        ["IVc","Cytotoxic CD8+ T cells, perforin/granzyme, FasL","SJS/TEN, fixed drug eruption, lichenoid drug eruption"],
        ["IVd","T cells, IL-8/CXCL8, neutrophils","Acute generalised exanthematous pustulosis (AGEP)"],
      ], top=4.65, height=2.4, col_widths=[1.6,4.6,6.3], header_size=12.5, body_size=11)
footer(s)
notes(s, "Gell and Coombs classification remains a core viva topic. Be fluent reciting all four types with a "
      "dermatological example for each, then subdivide Type IV (Pichler's classification) with a severe cutaneous "
      "adverse reaction (SCAR) example for each subtype - IVa granulomatous/contact, IVb eosinophilic (DRESS-like), "
      "IVc cytotoxic (SJS/TEN, fixed drug eruption), IVd neutrophilic (AGEP). This framework directly explains "
      "the drug reaction spectrum, a frequently tested clinical topic. Reference: Bolognia Ch. on Cutaneous Drug "
      "Reactions; Rook's Ch. on Adverse Cutaneous Drug Reactions.")

# =====================================================================
# SLIDE 16 - disease pathogenesis diagrams
# =====================================================================
s = add_slide(); header(s, "Synthesis", "Immunopathogenesis of Major Inflammatory Dermatoses", 16)
rows = [
    ("Psoriasis", ["Trigger/injury\n(Koebner, strep)", "Keratinocyte\nDAMPs + LL-37", "Dermal DC:\nIL-23/IL-12", "Th17/Th22\nIL-17, IL-22", "Keratinocyte\nhyperproliferation"], 1.5),
    ("Atopic dermatitis", ["Barrier defect\n(filaggrin)", "Alarmins\nTSLP, IL-33, IL-25", "DC/ILC2\nactivation", "Th2\nIL-4, IL-13, IL-31", "Pruritus + further\nbarrier breakdown"], 2.55),
    ("Allergic contact dermatitis", ["Hapten penetrates\nbarrier", "LC/dDC uptake\n+ migration", "Sensitisation:\nT-cell priming (LN)", "Re-exposure:\nelicitation", "Th1/CD8+ mediated\neczematous reaction"], 3.6),
    ("Urticaria", ["Trigger (allergen,\nautoantibody, physical)", "Mast cell/basophil\nactivation", "Histamine,\nleukotrienes, PAF", "Vasodilation +\nvascular leak", "Wheal & flare,\nangioedema"], 4.65),
    ("Acne", ["C. acnes +\nsebum/comedone", "TLR2 activation\n(keratinocyte/monocyte)", "IL-1\u03b2, inflammasome", "Neutrophil\nrecruitment", "Inflammatory\npapule/pustule"], 5.7),
]
for name, steps, top in rows:
    txt(s, 0.4, top, 1.55, 0.85, name, size=12.5, color=NAVY, bold=True)
    flow_row(s, steps, top=top, left=2.05, total_width=10.75, box_h=0.85, size=9.3, colors=[BOX1,BOX2,BOX3,BOX4,BOX5], gap=0.25)
footer(s)
notes(s, "Use this slide as a rapid visual recap connecting mechanism directly to five classic dermatoses. "
      "Psoriasis: LL-37-DNA/keratin17 self-antigens \u2192 dermal DC IL-23 \u2192 Th17/Th22 \u2192 IL-17/IL-22 act on "
      "keratinocyte IL-17RA/IL-22R1 \u2192 hyperproliferation, parakeratosis, Munro microabscesses. Atopic "
      "dermatitis: barrier defect \u2192 alarmins \u2192 Th2 skewing \u2192 IL-4/13 further suppress barrier genes "
      "(filaggrin, loricrin) - a self-amplifying loop, plus IL-31 driving itch. Allergic contact dermatitis: "
      "classic Type IV hypersensitivity with sensitisation and elicitation phases. Urticaria: mast-cell centred, "
      "IgE or non-IgE (autoimmune anti-FcεRI, physical, complement-mediated). Acne: innate-immune driven "
      "inflammatory disease, not purely a follicular/bacterial problem - explains why anti-inflammatory therapy "
      "(not just antibacterial) matters.")

# =====================================================================
# SLIDE 17 - leprosy
# =====================================================================
s = add_slide(); header(s, "Infection Immunology", "Immunology of Infection and the Leprosy Spectrum", 17)
bullets(s, [
    ("Host-pathogen interaction determines clinical phenotype far more than organism virulence alone - leprosy is the classic dermatological teaching model", 0, True),
    ("Innate recognition of M. leprae lipoproteins via TLR2/1; downstream cell-mediated (Th1) vs. humoral/Th2-skewed response determines disease pole", 0),
], size=15.5, top=1.35, height=1.5)
flow_row(s, ["TT\nTuberculoid", "BT", "BB\nMid-borderline", "BL", "LL\nLepromatous"], top=3.0,
         colors=[BOX1,BOX2,BOX3,BOX4,BOX5], size=13, box_h=0.75)
table(s, ["Feature","TT pole","LL pole"],
      [
        ["Immune response","Strong Th1/CMI, IFN-\u03b3, TNF-\u03b1","Weak CMI, Th2-skewed, T-cell anergy to M. leprae"],
        ["Bacillary load","Paucibacillary (few/absent bacilli)","Multibacillary (numerous bacilli, high antibody titres)"],
        ["Histology","Well-formed epithelioid granulomas, few lymphocytes at margin","Diffuse macrophage (foamy/Virchow cell) infiltrate, no granuloma"],
        ["Clinical lesions","Few, well-defined, hypoaesthetic plaques","Numerous, symmetric, poorly-defined nodules/infiltration"],
      ], top=4.0, height=2.35, col_widths=[2.3,5.0,5.2], header_size=12.5, body_size=11)
txt(s, 0.55, 6.55, 12.2, 0.75,
    "Immunological reactions: Type 1 (reversal) reaction - shift toward Th1/TT pole, delayed hypersensitivity flare in borderline disease; "
    "Type 2 reaction (ENL) - immune-complex (Type III-like) mediated, seen in BL/LL with high antigen load.", size=12.5, color=GOLD, bold=True, italic=True)
footer(s)
notes(s, "Leprosy is the single best clinical model of a Th1-Th2 immunological spectrum disease and is almost "
      "guaranteed to be asked in a dermatology viva. The Ridley-Jopling classification maps directly onto host "
      "immune polarity: strong cell-mediated (Th1/IFN-\u03b3) immunity contains the organism at the tuberculoid pole "
      "with granuloma formation and low bacillary index; weak CMI with T-cell anergy and a Th2-skewed/humoral "
      "response allows uncontrolled bacillary multiplication at the lepromatous pole. Type 1 (reversal) reactions "
      "reflect abrupt improvement in cell-mediated immunity (a delayed hypersensitivity-like flare) and occur in "
      "borderline patients, sometimes precipitated by treatment. Type 2 reactions (erythema nodosum leprosum) are "
      "immune-complex/Th2-cytokine driven (TNF-\u03b1 surge), occurring in BL/LL disease with high antigen load. "
      "Reference: Bolognia Ch. on Leprosy; Rook's Ch. on Leprosy; IJDVL reviews.")

# =====================================================================
# SLIDE 18 - therapeutics table
# =====================================================================
s = add_slide(); header(s, "Translational Immunology", "Immunology and Modern Dermatological Therapeutics", 18)
table(s, ["Pathway","Drug Class","Example(s)","Disease(s)"],
      [
        ["TNF-\u03b1","TNF inhibitor","Adalimumab, infliximab, etanercept","Psoriasis, PsA, HS, pyoderma gangrenosum"],
        ["IL-17A","IL-17 inhibitor","Secukinumab, ixekizumab, bimekizumab (IL-17A/F)","Psoriasis, PsA, axial spondyloarthritis"],
        ["IL-23 (p19)","IL-23 inhibitor","Guselkumab, risankizumab, tildrakizumab","Psoriasis, PsA"],
        ["IL-12/23 (p40)","IL-12/23 inhibitor","Ustekinumab","Psoriasis, PsA, Crohn's disease"],
        ["IL-4R\u03b1 (IL-4/IL-13)","Biologic (mAb)","Dupilumab","Atopic dermatitis, CRSwNP, asthma"],
        ["IL-13","Biologic (mAb)","Tralokinumab, lebrikizumab","Atopic dermatitis"],
        ["IL-31RA","Biologic (mAb)","Nemolizumab","Prurigo nodularis, AD (itch)"],
        ["JAK1/JAK2/JAK3","JAK inhibitor (oral/topical)","Tofacitinib, upadacitinib, abrocitinib, ruxolitinib (topical)","Atopic dermatitis, alopecia areata, vitiligo, PsA"],
        ["PDE4","PDE4 inhibitor","Apremilast, roflumilast (topical)","Psoriasis, PsA, oral ulcers of Beh\u00e7et"],
        ["Calcineurin/NFAT (T-cell)","Calcineurin inhibitor","Tacrolimus, pimecrolimus (topical); ciclosporin (systemic)","Atopic dermatitis, psoriasis (ciclosporin)"],
        ["CD20 (B cells)","B-cell depletion","Rituximab","Pemphigus vulgaris/foliaceus"],
      ], top=1.4, height=5.55, col_widths=[2.1,2.4,3.9,3.6], header_size=12, body_size=10)
footer(s)
notes(s, "This slide operationalises the talk's core message: 'from understanding the pathway to targeting the "
      "pathway.' Walk through it top-down following the same cytokine order as slide 10/9, so the story is "
      "coherent: TNF was the first major biologic target; the IL-23/Th17 axis then refined psoriasis therapy "
      "(IL-23 blockers now preferred for durability and safety over IL-12/23 blockade); the Th2 axis transformed "
      "atopic dermatitis treatment (dupilumab); JAK inhibitors act downstream of many cytokine receptors "
      "(cytokines signal via JAK-STAT) explaining their broad efficacy across atopic dermatitis, alopecia areata "
      "and vitiligo; rituximab depletes CD20+ B cells, reducing pathogenic anti-desmoglein antibody production in "
      "pemphigus. Be ready to explain why anti-IL-17 can unmask/worsen mucocutaneous candidiasis (IL-17 is "
      "essential for anti-fungal mucosal immunity) - classic viva question.")

# =====================================================================
# SLIDE 19 - integration/viva quick review
# =====================================================================
s = add_slide(); header(s, "Rapid Review", "High-Yield Integration + Quick-Fire Concepts", 19)
items = [
    "Skin = immune organ: barrier + innate + adaptive + SALT, resident memory T cells outnumber those in circulation",
    "Keratinocytes: express PRRs, secrete alarmins/cytokines/AMPs - active immunocytes, not passive structure",
    "Langerhans cell (epidermal, antigen capture) vs. dermal DC (dermal, major IL-23/IL-12 source)",
    "CLA + CCR4/CCR10 = skin-homing code; E-selectin/CCL17/CCL27 are the vascular address",
    "TRM cells = long-term local memory \u2192 explains fixed-site disease recurrence",
    "Th1 (IFN-\u03b3) vs Th2 (IL-4/13) vs Th17 (IL-17/22, IL-23-dependent) - map cytokine to disease instantly",
    "IL-23/IL-17 axis = backbone of psoriasis pathogenesis and the most successful biologic target class",
    "LL-37 (cathelicidin): antimicrobial + self-DNA complex \u2192 TLR9 \u2192 pDC activation \u2192 early psoriasis trigger",
    "Type IV hypersensitivity subtypes: IVa (Th1/macrophage), IVb (Th2/eosinophil), IVc (CD8 cytotoxic), IVd (neutrophilic/AGEP)",
    "Psoriasis = Th17-driven; Atopic dermatitis = barrier defect + Th2-driven (two ends of one spectrum concept)",
    "Leprosy spectrum = clinical readout of host Th1 (tuberculoid) vs. Th2/anergic (lepromatous) immune polarity",
    "Modern biologics/JAKi = direct pharmacological translation of the cytokine pathways discussed today",
]
box = s.shapes.add_textbox(Inches(0.55), Inches(1.4), Inches(12.3), Inches(5.6))
tf = box.text_frame; tf.word_wrap = True
for i, it in enumerate(items):
    p = tf.paragraphs[0] if i == 0 else tf.add_paragraph()
    p.space_after = Pt(8)
    r1 = p.add_run(); r1.text = f"{i+1}.  "; r1.font.bold = True; r1.font.color.rgb = GOLD; r1.font.size = Pt(14.5)
    r2 = p.add_run(); r2.text = it; r2.font.size = Pt(14.5); r2.font.color.rgb = DARK
footer(s)
notes(s, "Use this slide as your final rapid-fire recap before opening the floor to questions - each line is "
      "phrased as a ready-made 30-second answer. This is also effectively a preview of the viva question bank "
      "that follows in the appendix, so faculty questions asked from this slide should feel already anticipated.")

# =====================================================================
# SLIDE 20 - take home + references
# =====================================================================
s = add_slide(); header(s, "Summary", "Take-Home Messages and References", 20)
th = [
    "Skin is a complete immune organ - barrier, innate and adaptive arms act together, not in isolation",
    "Keratinocytes are active immune participants, not passive bystanders",
    "Langerhans cells and dermal DCs bridge innate sensing to adaptive, antigen-specific T-cell responses",
    "CLA-dependent trafficking and TRM cells explain skin-specific and site-specific immune memory",
    "The Th1/Th2/Th17/Th22/Treg framework explains the majority of inflammatory dermatoses",
    "The IL-23/Th17 axis is central to psoriasis; barrier defect + Th2 skewing is central to atopic dermatitis",
    "Hypersensitivity classification (Gell-Coombs, Type IV subtypes) explains most drug eruptions",
    "Loss of tolerance underlies pemphigus, pemphigoid, lupus, dermatomyositis and vitiligo",
    "Leprosy remains the best clinical model of the Th1-Th2 immunological spectrum in dermatology",
    "Modern biologics/JAK inhibitors are direct translations of cytokine pathway science into targeted therapy",
]
bullets(s, [(t,0) for t in th], top=1.4, height=3.55, size=14.5)
txt(s, 0.55, 5.05, 12.2, 0.3, "Primary References", size=15, color=NAVY, bold=True)
refs = [
    "Bolognia JL, Schaffer JV, Cerroni L. Dermatology, 5th Edition. Elsevier, 2024.",
    "Griffiths CEM, Barker J, Bleiker T, Chalmers R, Creamer D (eds). Rook's Textbook of Dermatology, 9th Edition. Wiley-Blackwell, 2016 (with ongoing online updates).",
    "Kabashima K, Honda T, Ginhoux F, Egawa G. The immunological anatomy of the skin. Nat Rev Immunol. 2019;19:19-30.",
    "Lande R, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature. 2007;449:564-9.",
    "Nograles KE, et al. Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. Br J Dermatol. 2008.",
    "Indian Journal of Dermatology, Venereology and Leprology - relevant reviews on leprosy immunology and psoriasis therapeutics (IJDVL, various years).",
]
box = s.shapes.add_textbox(Inches(0.55), Inches(5.4), Inches(12.3), Inches(1.9))
tf = box.text_frame; tf.word_wrap = True
for i, r in enumerate(refs):
    p = tf.paragraphs[0] if i == 0 else tf.add_paragraph()
    p.space_after = Pt(3)
    p.text = f"{i+1}. {r}"
    p.font.size = Pt(11); p.font.color.rgb = DARK
footer(s)
notes(s, "Close by reiterating the arc of the talk: barrier \u2192 innate \u2192 antigen presentation \u2192 T-cell "
      "polarisation \u2192 cytokine networks \u2192 clinical disease \u2192 targeted therapy. State clearly that Bolognia "
      "5th edition (2024) and Rook's 9th edition (Wiley-Blackwell, with online updates) were used as the primary "
      "frameworks, supplemented by key primary literature (Nature Reviews Immunology, Journal of Investigative "
      "Dermatology, British Journal of Dermatology) for mechanistic depth and IJDVL for regional relevance "
      "(leprosy). Thank the panel and invite questions.")

prs.save("/tmp/workspace/skin-immunology-ppt/Skin_Immunology_PGT1.pptx")
print("CORE_20_SAVED", len(prs.slides.__iter__.__self__._sldIdLst))

Successfully replaced 1 instance(s) of the string in '/tmp/workspace/skin-immunology-ppt/generate_ppt.py'