Section 1 Flashcards
DiGeorge syndrome lymphatic abnormality
Underdeveloped paracortex
Lymph drainage (top to bottom)
Cervical Hilar Mediastinal Axillary Celiac Superior mesenteric Inferior mesenteric Internal iliac Para-aortic Superficial inguinal Popliteal
- *Right lymphatic duct drains right body above diaphragm
- *Thoracic duct drains everything else into junction of left subclavian and internal jugular veins
Spleen organization
White pulp inside rings of red pulp with “barrel hoop” BM
White pulp: contains T cells in periarteriolar lymphatic sheath + B cells in follicles
Marginal zone is between red and white, contains APCs and specialized B cells
Macrophages found nearby remove encapsulated bacteria and IgM –> complement activation –> opsonization of it and killing of encaps bacteria
Vasculature and RBCs in red pulp
Examples of PAMPs
Pattern-associated molecular patterns recognized by PRRs (eg Toll-like receptors):
ex: LPS (G- bacteria), flagellin (bacteria), ssRNA (viruses)
MHC I vs MHC II
MHC I encoded by HLA-A, B, C genes
Binds TCR and CD8 receptor - presents endogenous antigens (intracellular material) to CD8+ cytotoxic T cells (delivered to MHCI in RER by TAP)
MHC II encoded by HLA-Ds, presents exogenous antigen to CD4+ cells
HLA A3 mutation
Hemochromatosis
HLA B27 mutation
PAIR:
Psoriatic arthritis
Ankylosing spondylitis
arthritis of IBD
Reactive arthritis/Reiter syndrom
HLA DQ2/DQ8 mutation
Celiac
HLA DR2
MS, hay fever, SLE, Goodpasture
HLA DR3
T1 DM, SLE, Graves, Hashimoto thyroiditis
HLA DR4
RA, T1DM
HLA DR5
Pernicious anemia, Hashimoto thyroiditis
Three ways to induce NK cells to kill
- Exposure to nonspecific activation signal on target cell
- Lack of MHCI on target cell surface
- CD16 binds Fc region of antibody-antigen complex, activating NK cell
Treg surface receptors
CD3, CD4, CD25, FOXP3
Make anti-inflamm cytokines (eg IL-10)
Th1 (helper T) - activated by ___, activates ____, inhibited by
- activated by IFN-gamma and IL-12
- activates macrophages and CD8 cells by secreting IFN-gamma
- inhibited by IL-4 and 10 (from Th2)
Th2 (helper T) - activated by ___, activates ___, inhibited by ___
- activated by IL-4
- secretes IL-4,5,10,13 to recruit eos and promote IgE production to fight parasites
- inhibited by IFN-gamma (from Th1)
T and B cell activation steps
APC (dendritic cell) samples and processes antigen –> lymph node –> presents antigen via MHC to activate T cell via TCR and costim (B7 on dendritic cell binds CD28 on T cell) –> T cell activated
Activated Th finds B cell that has picked up the antigen and binds/activates it; costim = CD40 rec (on B cell) and CD40L (on Th) –> turns B on –> class switching, affinity maturation, Ig production
Lymph node organization
Follicle - B cell (primary = dormant; 2ary = active, pale centers)
Medulla - cords (lymphs and plasma cells) and sinuses (retics and macrophages)
Paracortex (T cells, expands during CMI, contains HEV)
IgM
Produced in primary (immediate) response to antigen
Doesn’t cross placenta!
Switches isotype in lymph nodes via gene rearrangement –> IgA, IgE, IgG
IgG
Secondary (delayed) response to antigen
Crosses the placenta –> passive immunity
Fixes complement –> opsonization, neutralizes bacterial toxins and viruses
Thymus-dependent vs -independent antigens
Dependent: antigen contains protein component so can be processed and presented to B cells by Th1 –> memory B cells
Independent: antigens lack peptide component (eg LPS) so can’t be presented by MHC to T cells –> weakly or nonimmunogenic
Acute phase reactants are made in the ___ and induced by ___
Liver, IL-6
Acute-phase reactants
CRP (opsonin) Ferritin (sequesters iron) Fibrinogen (coag, endoth repair) Hepcidin (prevents release of iron bound by Ferritin) Serum amyloid A
Decreased with inflamm:
Albumin (saves AAs for increased reactants)
Transferrin (less of it –> sequestration of iron)
Complement pathways
Classic - IgG/M complexes (G- opsonization; starts with C1)
Lectin - mannose and lectin on bacterial surfaces (pathway starts with C1-like complex and C4 –> C3 convertase)
Alternative respond to microbial surfaces (pathway starts with C3)
All end in C3 –> C3b –> C4b2b3b (C5 convertase) which turns C5 into C5b, at which point C6-9 enter and form the membrane attack complex (MAC)
Inhibitors of complement on self cells
Delay-accelerating factor (DAF, aka CD55)
C1 esterase inhibitor
C1 esterase inhibitor deficiency
Can’t inhibit complement, Get Hereditary angioedema
ACEi contraindicated
C3 deficiency
Increases risk of infection and susceptibility to type 3 hypersensitivity
C5-C9 deficiency
Increased susc to recurrent Neisseria bacteremia
Cytokines (ILs)
Hot T-bone stEAK
IL-1: fever, secreted by macrophages (OC activating, acute inflamm, activates endothelium to express adhesion mcs + induce chemokines to recruit WBCs)
IL-2: stimulate T cells (secreted by T cells)
IL-3: stimulate bone marrow (secreted by T cells)
IL-4: stimulate IgE production (induces differentiation of T cells to Th2, secreted by Th2 cells, enhances class switching to IgE)
IL-5: stimulate IgA production +growth of eos, promotes differentiation of B cells, secreted by Th2 cells
IL-6: produce aKute-phase proteins and causes fever, secreted by macrophages
IL-8: Chemotactic factor for neutrophils, secreted by macrophages
IL-10: attenuates immune response, secreted by Th2 (decreased expression of MHC II and Th1 cytokines, inhibits APCs)
IL-12: released by macrophages -> T cells differentiate into Th1 and NK cells activated
TNF-alpha: activates endothelium –> septic shock
IFN-gamma: Th1 cells secrete it to activate macrophages and more NK cells (Th1)
Chronic granulomatous disease (CGD)
Defective enzymes (especially NADPH oxidase) make phagocytic cells unable to generate ROS, which would activate the phagocytic cells –> kill bug
Rely on bug to make ROS, so increased susc to bugs that neutralize their ROS (catalase positive bugs)
B7 surface protein
on APCs with MHCII, serves as co-stim second signal by binding to CD28 on T cells and thus activating them
CD40L
surface protein on Helper T cells (CD4+) that serves as co-stim second signal, activating B cells and macrophages
CD21
EBV receptor on B cells
CD 19, 20, 21
surface proteins on B cells
CD14
macrophage surface protein - directly stimulated by endotoxins/LPS (G-) –> phagocytosis of bug
aka TLR4
CD16
NK cell surface protein - binds Fc of IgG
CD56
unique marker for NK cells (surface protein)
CD34
hematopoeitic stem cell surface protein
Examples of live attenuated vaccine
MMR, Polio (Sabin), Varicella, Flu (intranasal), Yellow fever
Examples of inactivated or killed vaccine
Rabies, Influenza (IM), Polio (Salk), Hep A
Type I hypersensitivity
Antigen binds preformed (fast) IgE, which is cross-linked and bound to pre-sensitized mast cells and basophils
Binding –> release of vasoactive amines (eg histamine)
Type II hypersensitivity
IgM, IgG bind antigen that’s fixed to cell and target that cell for destruction by complement, opsonization/phag, or antibody-mediated cell dysfxn
Test with Coombs (direct - Ig on RBCs, or indirect - serum Ig that can adhere to RBCs)
Type III hypersensitivity
Ag-Ig complexes form, bind complement, and attrack PMNs, which release lysosomal enzymes
Serum sickness - complexes deposited in membranes, fix complement there and –> tissue damage within 5-10 days of exposure, fever, urticaria, arthralgia etc
Arthus rxn = serum sickness but in skin (antigen = intradermal)
Type IV hypersensitivity
Delayed, T cell mediated
T cells find antigen and release cytokines –> activate macrophages (no Ig involved)
Hypersensitivity disorders
Type I - rhinitis, hay fever, eczema, anaphylaxis (eg bee sting)
Type II - AIHA, bullous pemphigoid, Goodpasture, Graves, Guillain-Barre, MG, pemphigus vulgaris, pernicious anemia, RF
Type III - Arthus, Serum sickness, SLE, PSGN
Type IV - Contact dermatitis, GVHD, MS, PPD
Aldesleukin
Recombinant IL2 used to treat RCCA and metastatic melanoma
Filgrastim and Sargramostim (“-stim”)
Recombinant G(M)-CSF used for bone marrow recovery
IFN-alpha
Chronic hepatitis, Kaposi sarcoma, malignant melanoma
IFN-beta
MS
IFN-gamma (treats what?)
CGD
Recombinant cytokines used to treat thrombocytopenia
Romiplostim, eltrombopag, Oprelvekin (IL-11)
CD28
costim receptor on T cells, binds to B7 on APC
