Ok Seriously (get to studying Immunology)

CD3

Marker for all T cells

CD4

Marker for helper T cells

CD8

Marker for cytotoxic T cells

CD19 and CD20

Markers for B cells (lost when B cells become plasma cells)

CD16

NK cell receptor that binds Fc of IgG, mediates ADCC

CD56

Marker used to identify NK cells

Treg markers

CD4, CD25, CTLA-4, FoxP3

Monocytes

Circulate briefly then differentiate into macrophages, which persist >12 months in tissue

Langerhans cells

Dendritic cells specific to the skin (epidermis)

Follicular dendritic cells

Display antigen to B cells in germinal centers (distinct from classical dendritic cells)

Basophils

Granulocyte, stains blue, releases histamine

Eosinophils

Granulocyte, stains red with eosin, fights parasites

Neutrophils

Most abundant granulocyte, short-lived (6-8 hrs), first responders to bacteria

IL-2

From activated T cells (autocrine); drives T cell proliferation, Treg survival, NK activation

IL-3

Induces maturation of all hematopoietic lineages from immature progenitors

IL-4

From Th2 cells/mast cells; drives B cell switching to IgE, Th2 differentiation, alternative macrophage activation

IL-5

From Th2 cells; activates and increases eosinophils

IL-6

From macrophages/endothelial cells/T cells; stimulates liver acute phase proteins, B cell proliferation

IL-7

Drives proliferation/survival of early T and B cell progenitors and naive/memory T cells

IL-10

Anti-inflammatory; supports Treg development/survival; inhibits macrophage activation

IL-12

From macrophages; drives Th1 differentiation and IFN-γ release from Th1/NK cells

IL-13

From Th2 cells; B cell switching to IgE, alternative macrophage activation, mucous secretion

IFN-γ

From Th1, CD8 T cells, NK cells; most potent macrophage activator

IL-17

From Th17 cells; stimulates acute inflammation, neutrophil recruitment

IL-21

From T follicular helper cells; B cell activation, Tfh differentiation

IL-22

From Th17 cells, NK cells, ILCs; maintains epithelial barrier integrity

TNF-α

Key inflammatory cytokine; recruits inflammatory cells, activates macrophages (blocked by infliximab/etanercept)

GCSF and GMCSF

Growth factors driving neutrophil production/expansion

Th1 differentiation

Driven by IL-12 (from macrophages), signature cytokine IFN-γ

Th2 differentiation

Driven by IL-4, signature cytokines IL-4, IL-5, IL-13

Th17 differentiation

Driven by IL-1, IL-6, IL-23, signature cytokines IL-17, IL-22

IgA class switching cytokines

TGF-β, IL-5, TNF-family cytokines (reduced by IFN-γ and IL-4)

TLR1, 2, 6

Recognize bacterial lipopeptides (gram positive); TLR2 also peptidoglycan

TLR3

Recognizes viral dsRNA

TLR4

Recognizes LPS (gram negative bacteria)

TLR5

Recognizes bacterial flagellin

TLR7 and TLR8

Recognize viral ssRNA

TLR9

Recognizes CpG DNA (bacteria, viruses, fungi)

MHC I

Presents peptides made inside the cell to CD8 T cells

MHC II

Presents peptides from engulfed material to CD4 T cells

MHC I expression

All nucleated cells

MHC II expression

Antigen-presenting cells (dendritic cells, macrophages, B cells)

Human HLA genes

Encoded on chromosome 6 (class I

B7 (CD80/CD86)

Binds CD28 on T cell to activate, or CTLA-4 to inhibit

CD40-CD40L

Costimulatory signal between T cell (CD40L) and B cell (CD40) needed for B cell activation

LFA-1 and ICAM-1

LFA-1 (integrin on T cells) binds ICAM-1 on APCs, stabilizes the interaction

PD-1/PDL-1

Inhibitory checkpoint; PD-1 on T cells binds PDL-1 (often on tumor cells), reduces T cell activity

IgM

First antibody made in a primary response; activates classical complement; pentamer

IgG

Crosses the placenta, provides neonatal immunity, main serum antibody

IgA

Dominant mucosal antibody (gut/respiratory), dimer, transported by poly-Ig receptor

IgE

Drives mast cell degranulation and anti-parasite defense

IgD

Naive B cell receptor only, no known secreted effector function

IgG subclasses

4

IgA subclasses

2

AID

Enzyme (activation-induced cytidine deaminase) that drives isotype/class switching

Somatic hypermutation

Increases antibody affinity over time, occurs in germinal centers

Classical complement pathway trigger

Antibody (IgM or IgG) bound to antigen activates C1

Alternative complement pathway trigger

Spontaneous low-level hydrolysis of C3, amplified on microbial surfaces

Lectin complement pathway trigger

Mannose-binding lectin binding microbial carbohydrates

Classical/lectin C3 convertase

C4b2a

Alternative C3 convertase

C3bBb, stabilized by properdin

C3 cleavage products

C3a (inflammation) and C3b (opsonization, forms C5 convertase)

C5 cleavage products

C5a (inflammation) and C5b (initiates membrane attack complex)

Membrane Attack Complex

C5b + C6 + C7 + C8 + polymerized C9, forms a pore causing osmotic lysis

C1 inhibitor deficiency

Hereditary angioedema

DAF deficiency

Paroxysmal nocturnal hemoglobinuria

Factor H/Factor I deficiency

Atypical hemolytic uremic syndrome; also age-related macular degeneration

C3 deficiency

Severe, potentially fatal recurrent bacterial infections

C9/MAC deficiency

Increased susceptibility to Neisseria infections

CRP

Binds phosphorylcholine on microbes, opsonizes for phagocytosis, activates classical complement

B cell maturation site

Bone marrow

T cell maturation site

Thymus

Double-positive T cells binding self-MHC too strongly

Negative selection, apoptosis (or receptor editing)

Double-positive T cells with no self-MHC recognition

Death by neglect (apoptosis), failed positive selection

CD4 vs CD8 commitment

Determined by recognition of MHC II (CD4 retained) vs MHC I (CD8 retained)

Central B cell tolerance outcomes

Receptor editing (light chain re-rearrangement) or apoptosis

Anergy

Functional inactivation of a lymphocyte from antigen recognition without costimulation

Peripheral T cell tolerance mechanisms

Anergy, deletion, suppression by regulatory T cells

Checkpoint inhibitor drugs

Anti-CTLA-4 (ipilimumab), anti-PD-1 (nivolumab, pembrolizumab)

CD8 T cell full differentiation requirement

CD4 T cell help in addition to antigen recognition

HIV and CD8 responses

Defective because CD8 T cells need CD4 T cell help to fully activate

Type I hypersensitivity

IgE-mediated mast cell activation, minutes to hours

Type II hypersensitivity

IgG against cell-bound antigen, e.g. autoimmune cytopenias

Type III hypersensitivity

Antigen-antibody immune complexes deposit in tissue, e.g. serum sickness, 1-3 weeks

Type IV hypersensitivity

T cell mediated, delayed days-weeks, e.g. contact dermatitis, SJS/TEN, DRESS, AGEP

Anaphylaxis diagnostic criteria

Skin/mucosal symptoms plus hypotension/respiratory compromise/GI symptoms, or known allergen exposure plus those systemic symptoms

Anaphylaxis first-line treatment

Epinephrine (IM); antihistamines/steroids treat symptoms only

Epinephrine receptor actions

β1 increases HR/contractility, β2 causes bronchodilation, α causes vasoconstriction/increased BP

SJS vs TEN

SJS

DRESS syndrome

Delayed onset (2-8 wks), slow resolution (>6 wks), fever, lymphadenopathy, eosinophilia, organ injury

Venom immunotherapy

Reduces anaphylaxis risk from ~80% to ~1%

Anti-dsDNA and anti-histone antibodies

Seen in systemic lupus erythematosus

Rheumatoid factor

Targets the Fc region of IgG

Anti-centromere antibodies

Seen in scleroderma

MHC class II and autoimmunity

Most disease associations involve class II because it controls CD4 T cell activation

Molecular mimicry

Cross-reaction between a pathogen antigen and self-antigen due to structural similarity

Cyclosporine A

Calcineurin inhibitor, blocks IL-2 production, blocks T cell proliferation

Infliximab/etanercept

TNF antagonists, block inflammation

Rituximab

Anti-CD20 antibody, depletes B cells, spares plasma cells/stem cells

Abatacept/belatacept

CTLA-4 agonist/fusion protein, blocks B7-CD28 costimulation