LAST DANCE LAST CHANCE

Classical complement pathway trigger

C1 binds antigen-antibody complex (IgG/IgM)

Lectin complement pathway trigger

Mannose-binding lectin binds mannose on microbe surface

Alternative complement pathway trigger

Spontaneous C3 hydrolysis, C3b binds pathogen directly

What all 3 complement pathways converge on

C3 convertase

C3b function

Opsonization - coats bacteria for phagocytosis

C3a and C5a function

Anaphylatoxins - mast cell degranulation, inflammation

C5a additional function

Most potent neutrophil chemotaxis signal

C5b-9 function

Membrane Attack Complex (MAC) - lyses pathogen, especially gram-negative

C1 esterase inhibitor deficiency causes

Hereditary angioedema

C3 deficiency causes

Severe recurrent pyogenic infections

C5-C9 (terminal/MAC) deficiency causes

Recurrent Neisseria infections specifically

DAF/CD55 deficiency causes

Paroxysmal nocturnal hemoglobinuria (PNH)

Toll-like receptors (TLRs) location

Plasma membrane and endosomal membrane

Toll-like receptors (TLRs) function

Bind PAMPs, trigger NF-kB, inflammatory cytokines

NOD-like receptors (NLRs) location

Cytosol

NOD-like receptors (NLRs) function

Sense intracellular bacterial products, form the inflammasome

Inflammasome function

Activates caspase-1, cleaves pro-IL-1beta to active IL-1beta

RIG-like receptors (RLRs) function

Sense viral RNA, trigger interferon production

IgG unique feature

Only antibody that crosses the placenta

IgG primarily targets

Systemic bacteria and viruses (long-term/secondary response)

IgM structure

Pentamer

IgM primarily targets

Bloodstream pathogens/bacteremia, first responder, best complement fixation

IgA structure and location

Dimer with secretory component; mucosal surfaces, breast milk

IgA primarily targets

Mucosal pathogens (GI, respiratory, GU tract)

IgE binds to

Mast cells and basophils

IgE primarily targets

Parasites/helminths; also drives Type I hypersensitivity/allergy

IgD function

Naive B cell surface antigen receptor

V(D)J recombination enzymes

RAG1 and RAG2

Enzyme that adds junctional diversity in V(D)J recombination

TdT (terminal deoxynucleotidyl transferase)

Somatic hypermutation occurs where

Germinal center, causes affinity maturation

Class switch recombination requires

CD40L-CD40 interaction plus cytokines

Cytokine that induces class switch to IgE

IL-4

Cytokine that induces class switch to IgG

IFN-gamma

MHC Class I expressed on

All nucleated cells

MHC Class I presents to

CD8+ T cells

MHC Class I antigen source

Endogenous (intracellular - viral, tumor) via proteasome and TAP transporter

MHC Class II expressed on

Professional APCs only (macrophages, dendritic cells, B cells)

MHC Class II presents to

CD4+ T cells

MHC Class II antigen source

Exogenous (extracellular, phagocytosed) via lysosomal degradation

CD4 binds

MHC Class II

CD8 binds

MHC Class I

Bare Lymphocyte Syndrome Type I defect

TAP1 or TAP2 mutation - no MHC I

Bare Lymphocyte Syndrome Type I presentation

Chronic respiratory infections, bronchiectasis, normal antibodies

Bare Lymphocyte Syndrome Type II defect

CIITA or RFX mutation - no MHC II

Bare Lymphocyte Syndrome Type II presentation

Defective CD4+ T cell development, SCID-like severe immunodeficiency

Positive selection occurs where

Thymic cortex

Positive selection function

T cells that weakly bind self-MHC survive; others die by neglect

Negative selection occurs where

Thymic medulla

Negative selection function

T cells that bind self-MHC+self-peptide too strongly are deleted (central tolerance)

Gene that controls negative selection

AIRE gene - drives expression of peripheral tissue antigens in thymus

AIRE gene deficiency causes

APECED/APS-1 (Autoimmune Polyendocrine Syndrome type 1)

APECED/APS-1 classic triad

Chronic mucocutaneous candidiasis, hypoparathyroidism, adrenal insufficiency

T cell activation Signal 1

TCR binds peptide-MHC complex

T cell activation Signal 2 (costimulation)

CD28 (T cell) binds B7/CD80-86 (APC)

T cell without costimulation signal becomes

Anergic (unresponsive)

CTLA-4 function

Inhibitory receptor, competes with CD28 for B7, downregulates T cell response

Th1 induced by

IL-12, IFN-gamma

Th1 produces

IFN-gamma

Th1 function

Activates macrophages, fights intracellular pathogens

Th2 induced by

IL-4

Th2 produces

IL-4, IL-5, IL-13

Th2 function

Activates eosinophils/B cells (IgE), fights parasites, allergy

Th17 induced by

IL-6, TGF-beta, IL-23

Th17 produces

IL-17

Th17 function

Neutrophil recruitment, fights extracellular bacteria/fungi

Treg induced by

TGF-beta, IL-2

Treg produces

IL-10, TGF-beta

Treg function

Immune suppression, peripheral tolerance, marker is FoxP3

T-dependent antigens

Protein antigens, need T cell help, get class switching/memory/affinity maturation

T-independent antigens

Polysaccharides (e.g. bacterial capsules), activate B cells directly, IgM only, no memory, weak response in kids under 2

Why conjugate vaccines exist

Attach polysaccharide to protein to recruit T cell help in young children

IL-1 source and function

Macrophages; fever, inflammation (endogenous pyrogen)

IL-2 source and function

Th cells; T cell proliferation

IL-6 source and function

Macrophages; fever, acute phase protein production in liver

IL-8 source and function

Macrophages; neutrophil chemotaxis

IL-10 source and function

Treg/macrophages; anti-inflammatory, inhibits Th1/macrophages

IL-12 source and function

Macrophages/DCs; drives Th1 differentiation, activates NK cells

TNF-alpha source and function

Macrophages; fever, inflammation, septic shock, cachexia

IFN-gamma source and function

Th1, NK, CD8 T cells; activates macrophages, increases MHC expression, antiviral

Live attenuated vaccine examples

MMR, Varicella, Oral polio (Sabin), Yellow fever, Rotavirus

Live attenuated vaccine contraindication

Pregnancy, immunocompromised patients

Inactivated/killed vaccine examples

Injectable polio (Salk), Hepatitis A, Rabies, Flu shot

Conjugate vaccine examples

Pneumococcal conjugate, Hib

Conjugate vaccine mechanism

Polysaccharide + protein carrier to recruit T cell help in children

Toxoid vaccine examples

Tetanus, Diphtheria

Toxoid vaccine mechanism

Inactivated toxin, generates antitoxin antibodies

X-linked agammaglobulinemia (Bruton) defect

BTK mutation, no B cell maturation

X-linked agammaglobulinemia (Bruton) presentation

Recurrent bacterial infections after ~6mo, no B cells, no tonsils

Selective IgA deficiency risk

Anaphylaxis to blood products (anti-IgA antibodies react to donor IgA)

DiGeorge syndrome defect

22q11 deletion, thymic aplasia

DiGeorge syndrome presentation

T cell deficiency, hypocalcemia (no parathyroids), cardiac defects - CATCH-22

X-linked SCID defect

IL2RG (common gamma chain) mutation

X-linked SCID presentation

T-B+NK- , severe combined immunodeficiency

ADA deficiency SCID mechanism

Adenosine deaminase deficiency causes toxic metabolite buildup

ADA deficiency SCID presentation

T-B-NK-

Wiskott-Aldrich syndrome defect

WASP gene, X-linked, cytoskeleton defect

Wiskott-Aldrich syndrome triad

Eczema, thrombocytopenia (small platelets), recurrent infections

Chronic Granulomatous Disease (CGD) defect

NADPH oxidase defect, no respiratory burst

Chronic Granulomatous Disease (CGD) presentation

Catalase-positive organism infections (Staph aureus, Aspergillus)

Chronic Granulomatous Disease (CGD) diagnostic test

Negative nitroblue tetrazolium (NBT) test