Immuno - basic Flashcards
Lymph node structureWhere are…B-cells?T-cells?Lymphos/plasma cells?Macs/retics?
fxn: nonspecific filtration by macs, lympho storage
follicle - B-cells! primary (outer) = dense/dormant. secondary (inner) = germinal centers, active
medulla - medullary cords (lymphos + plasma cells), sinuses (reticular cells, macs)
paracortex - houses T cells, T/B cells enter from blood, site of engorgement during immune response
Spleen sinusoidsWhere are…T cells?B cells?APCs?
Red pulp = mechanical filtration of RBCs by fenestrated BM and macs, led to trabeculae
White pulp =
- periarteriolar lymphatic sheath (PALS): T cells
- follicles: B cells
Marginal zone = APCs capture blood-borne antigens for recognition by lymphocytes
Post-splenectomy findings
Howell-Jolly bodies (nuclear remnants in an RBC)
Target cellsThrombocytosis
Thymus structure Where are... immature T cells? mature T cells? Where do positive and negative selection occur?
T-cell differentiation and maturation
derived from Third pharyngeal pouch
Cortex = immature T cells (site of positive selection: only T cells expressing TCRs that bind self-MHC survive) Medulla = pale, mature T cells (site of negative selection: T cells with TCRs for high-affinity self-antigen binding are apoptosed)
innate vs. adaptive immunity
innate - secreted proteins: lysozyme/complement/CRP, TLRs recognize PAMPs (LPS, flagellin, ssRNA)
adaptive - variation through VDJ recomb, based on Igs
MHC I
- MHC I: HLA-A, HLA-B, HLA-C, all nucleated cells
- present viral/cytosolic proteins to CD8 cells
- loading happens in RER- assoc with B-microglobulin
MHC II
- MHC II: HLA-DR, HLA-DP, HLA-DQ
- binds CD4
- expressed on APCs only
- loading happens in acidified endosome with invariant chain
HLA subtypes and disease
A3 - hemochromatosis
B27 - PAIR: psoriatic arthritis, ank spondy, IBS, reactive arthritis
DQ2/DQ8 - celiac disease
DR2 - multiple sclerosis, hay fever, SLE, Goodpasture
DR3 - DM Type I, SLE, Graves, Hashimoto
DR4 - DM Type I, Rheum (4 walls in a room)
DR5 - pernicious anemia
NK cells function, cytokines, signals for activation
Apoptosis induction (using perforin and granzymes)
Enhanced by IL-2, IL-12, IFN-a, IFN-B
2 signals: non-specific activation signal, absence of class I MHC
Helper T cells (CD4+)Th1 (phagocytosis/cell-mediated) vs. Th2 (antibody response)
Give activating and inhibiting cytokines
Th1 = secretes IFN-y, macs/cytotoxic T, activated by IFN-y and IL-12 (from macs), inhibited by IL-4/10 (from Th2)
Th2 = secretes IL-4/5/10/13, activate B cells and recruit eosinophils, activated by IL-4, inhibited by IFN-y (from Th1)
Cytotoxic T cells function
Release cytotoxic granules containing preformed proteins (perforin, granzyme) to induce apoptosis
Regulatory T cells
Maintain specific immune tolerance by suppressing CD4/CD8 T cells
Look for: CD3/4/25, FoxP3Produce IL-10, TGF-B
Naive T-cell activation
- DC samples/processes antigen
- DC migrates to draining lymph node
- MHC II/I presents foreign antigen to CD4/8
- Costimulatory signal is given by interaction of B7 and CD28 (if no second signal, then anergy)
- Th cell activates and produces cytokines. Tc cell activates and destroys
B-cell activation
- Th cell activation
- B-cell receptor mediated endocytosis, foreign antigen is presented to helper T
- CD40 receptor on B cell binds CD40L on helper T cell
- Helper T secretes cytokines to stimulate Ig class switching of B cell (IL-4, IL-5)
Antibody structure, function, diversity (3 mechs)
Light and heavy chains (light = Fab only, heavy = both),
Fc binds complement (one arm, Constant, Carboxy terminal, Complement, Carbo side chains)
Fab binds antigen (two arms)
Diversity: VJ/VDJ recomb, somatic hypermutation, terminal deoxynucleotidyl transferase (DNA nuc addition)
IgG
fixes complement, crosses placenta
IgA
prevents microbe attachment to mucous membranes, does not fix complement, produced in GI tract to protect against GI infxns, released in secretions as a dimer (notably breast milk)
IgM
immediate response to antigen, serves as antigen receptor to B cells, pentamer form allows avid binding to antigen
IgE
binds mast cells/basophils, cross-links when exposed to allergen, mediates Type I hypersensi rxn, mediates worm resistance through Eos
Acute phase reactants (produce in liver in response to inflammation, induced by IL-6)
Upregulated: CRP (fixes complement), ferritin (sequesters iron), fibrinogen (coagulation factor, correlates with ESR), hepcidin (prevents release of iron bound to ferritin, leads to AOCD)
Downregulated: albumin (reduction conserves amino acids for acute phase proteins), transferrin (sequester iron)
Complement pathways
Classic - IgG, IgM mediated (GM makes classic cars), C1
Alternative - microbe surface molecules, C3Lectin - mannose or other sugars on microbe surface, C1-like complex
Complement 3b
opsonization, C3b binds bacteria (also helps clear immune complexes)
Complement 3a/4a/5a
anaphylaxis (5a also does neut chemotaxis)
Complement 5b-9
cytolysis by MAC
Complement DAF
Inhibitors: DAF = CD55, combines with C1 esterase inhibitor to help prevent complement activation on self cells
Complement disorders
Hereditary angioedema
Severe pyogenic infections, incr. Type III hypersensitivity
Incr. Neisseria bacteremia
C1 esterase inhibitor deficiency (results in longer C1 half life) - ACEis are contraindicated
C3 deficiency
C5-C9 deficiencies
Important cytokines secreted by Macrophages
Hot T-Bone stEAK: 1 = fever 2 = stimulate T cells 3 = bone marrow (GM-CSF analog) 4= IgE 5= IgA 6= aKute phase reactants
IL-8: chemotaxis for neutrophils
IL-12: differentiation of T cells into Th1 cells, NK activator
TNF-a: septic shock, WBC recruitment, vascular leak
Important cytokines secreted by All T cells
IL-2: stimulate T cell maturation
IL-3: functions like GM-CSF
Important cytokines secreted by Th1 cells
IFN-y: stimulates macs to kill pathogens (also activates NK cells to kill virus-infected cells)
Important cytokines secreted by Th2 cells
IL-10: modulates inflammatory response, decreases cytokines, inhibits macs/DCs (works in concert with TGF-b)
Respiratory burst, NADPH oxidase, CGD
Activation of neutrophil NADPH oxidase, leads to rapid release of ROS/hypochlorite to kill microbes
In CGD, phagocytes don’t make their own peroxide (due to lack of NADPH oxidase) so they use microbial peroxide. However, microbes with their own catalase (which breaks down peroxide) survive! Watch for S. aureus and Aspergillus
Interferons
Glycoproteins synthesized by virus-infected cells that act locally on non-infected cells to ramp up viral defenses (selectively degrade viral nucleic acid/protein)
Essentially results in apoptosis
“Interfere with viruses”
Superantigens
cross-link beta-region of T-cell receptor to the MHC class II on APCs
- T cells (IL-2) and macrophages (IL-1 and TNF-a) lead to massive cytokine release
Endotoxins
Endotoxin: direct stimulation of macrophages by binding to endotoxin receptor TLR4/CD14
Antigenic variation
bacteria: Salmonella (flagella), Borrelia recurrentis (relapsing fever), N. gonorrheae (pilus)
viruses: influenza, HIV, HCV
parasites: trypanosomes
Administration of preformed antibodies
Passive immunity
Rapid onset
Tetanus, Botulinum, HBV, Varicella, Robies
ex: breast milk (IgA dimers), placental (IgG), antitoxin
Exposure to foreign antigens
Active immunity
slow onset, long-lasting protection
Vaccine with cellular and humoral responses
Live, attentuated vaccine
Microbe has lost pathogenicity but retains capacity for growth
Life long immunity
MMR, polio (sabin), intranasal flu, chicken pox, yellow fever
Vaccine with only humoral response
Inactivated/Killed vaccine
Epitope structure is maintained on surface antigens
Weaker immune response, booster shots required
RIP Always: Rabies, Influenza (shot), Polio (Salk), hep A
