Immunology Flashcards
1
Q
Lymph node- role
A
Many afferents + 1 or more efferents
Role: non-specific filtration by macrophages, storage of B and T cells and immune response activation
2
Q
Follicle
A
site of B cells (localization and proliferation)
Primary follicles (dormant and dense) Secondary follicles (active and have central pallor)
3
Q
Paracortex
A
Houses T cells. Contains high endothelial venues through with T and B cells ENTER from the blood
Not well developed in pts with DiGeorge syndrome
Paracortex enlarges in extreme cellular immune response (e.g. viral infection)
4
Q
Medulla
A
Medullary cords (closely packed lymphocytes and plasma cells) and medullary sinuses.
Medullary sinuses communicate with efferent lymphatics and contain reticular cells (fibroblasts that produce collage) and macrophages
5
Q
Cervical
A
Head and neck
6
Q
Hilar
A
Lungs
7
Q
Mediastinal
A
Trachea and esophagus
8
Q
Axillary
A
Upper limb, breast, skin above umbilicus
9
Q
Celiac
A
Liver, stomach, spleen, pancreas, and upper duodenum
10
Q
Superior mesenteric
A
Lower duodenum, jejunum, ileum, colon to splenic flexure
11
Q
Inferior mesenteric
A
Colon from splenic flexure to upper rectum
12
Q
Internal iliac
A
Lower rectum to anal canal (above pectinate) Bladder Vagina (middle 1/3) Cervix Prostate
13
Q
Para-aortic
A
Testes, ovaries, kidneys, uterus
14
Q
Superficial inguinal
A
Anal canal (below pectinate line)
Everything (including legs) below umbilicus (except popliteal area)
Scrotum
Vulva
15
Q
Popliteal
A
Dorsolateral foot
Posterior calf
16
Q
Right lymphatic duct
A
Drains right side of the body above diaphragm
17
Q
Thoracic duct
A
Drains everything into the junction of the left subclavian and internal jugular vein
18
Q
Sinusoids of the spleen
A
Red pulp- with fenestrate (barrel hoop) basement membrane
19
Q
Spleen- T cell location
A
found in the periarteriolar lymphatic sheet (PALS) within the white pulp
20
Q
Spleen- B cell location
A
found in the follicles within the white pulp
21
Q
Marginal zone
A
Between the red pulp and the white pulp
Contains macrophages and specialized B cells (where APCs capture blood-borne antigens for recognition by lymphocytes)
22
Q
Macrophages
A
Remove encapsulated bacteria
23
Q
Splenic dysfunction
A
E.g. post-splenectomy, sickle cell disease
Decreased IgM –> decreased complement activation –> decreased C3b opsonization –> increased susceptibility to encapsulated organisms
24
Q
Splenic dysfunction- Susceptible Organisms
A
“Please SHINe my SKiS”
Pseudomonas A. Strep pneumo Hemophilus Influenzae Neisseria meningitidis Salmonella sp Klebsiella pneumonia Group B Streptococci
25
Post splenectomy cells
Howell-Jolly bodies (nuclear remnant- RNA)
Target cells
Thrombocytosis (loss of sequestration and removal)
Lymphocytosis (loss of sequestration)
26
Thymus
Located in the anterosuperior mediastinum
Site of T-cell differentiation and maturation
Thymus is derived from "Thyrd" pharyngeal pouch
Lymphocytes- mesenchymal origin
Cortex- dense with immature T cells; Medulla- pale with mature T cells and Hassall corpuscles continue epithelial reticular cells (secrete thymic hormones??)
27
T cells vs. B cells
T cells = Thymus
| B cells = Bone marrow
28
Hypoplastic/hyperplastic thymus
Hypoplastic- Seen in diGeorge and SCID
| Enlarged- in myasthenia gravis
29
Innate immunity
Components: Mphages, neutrophils, monocytes, dendritic cell, NK cells, complement
Encoded by gremlin
Rapid response to pathogens, non-specific
Secretes: lysozymes, complment, C-reactive protein, defensins
Toll-like receptors: pattern recognition receptors that PAMPs (e.g. LPS (gram neg bacteria), flagellin (bacteria), nucleic acids (viruses))
30
Adaptive immunity
Components: T cells, B cells, and circulating antibodies
Variation through VDJ recombination during lymphocyte development
Highly specific; develops over long periods (memory response is faster and more robust)
Secretes: immunoglobulins
Memory cells: activated by B and T cells; subsequent exposure to a previously encountered antigen --> stronger, quicker immune response
31
MHC I and II
Encoded by HLA genes and present antigen fragments to T cells
32
MHC class I
HLA- A, B and C
Bind to TCR and CD8
Expressed on ALL nucleated cells (therefore not RBCs)
Present ENDOGENOUSLY synthesized antigens (viral or cytosolic proteins) to CD8+ cytotoxic T cells
Antigen peptides loaded onto MHC I in RER after delivery via TAP (transporter associated with antigen processing)
Associated proteins: beta-2 microglobulins (3 alpha chains and 1 beta globulin)
Viral infection activate and up regulate MHC Class I molecules
33
MHC class II
HLA DP, DQ, DR
Bind to TCR and CD4
Expressed on APCs
Present exogenously synthesized antigens (bacterial proteins) and to CD4+ helper T cells
Antigen loaded following the release of invariant chain (2 alpha and 2 beta chains) in an acidified endosome
Invariant chain is digested by Mphages during antigen processing
34
HLA A3
Hemochromatosis
35
HLA B8
Addison disease, myasthenia gravis
36
HLA B27
PAIR (seronegative arthropathies): Ankylosing spondylitis, Reactive arthritis, Psoriatic arthritis, IBD associated arthritis
37
HLD DQ2/DQ8
Celiac
38
DR2
MS, hay fever, SLE, Goodpastures
39
DR3
DM type I, SLE, Graves, Hashimoto thyroiditis, Addison (also B8)
40
DR4
RA (4 walls in a rheum), DM type I, Addison (also B8 and DR3)
41
DR5
Pernicious anemia (B12 def), Hashimoto thyroiditis
42
NK cells
Part of the INNATE immune system
Use perforin and granzymes to INDUCE APOPTOSIS of virally infected and tumor cells
Induced to kill when exposed to a activation signal on target cell or an ABSENCE of MHC class I on target cell surface (e.g tumor cells)
Also kills via antibody-dependent cell-mediated cytotoxicity (CD16 binds Fc region of bound Ig, activating the NK cell)
43
B cell functions
Recognize antigen (then undergo somatic hypermutation to optimize antigen specificity)
Produce antibody (differentiate into plasma cell to secrete specific Ig)
Maintain immunologic memory- memory B cells persist (for accelerated future response to antigen)
44
T cell functions
CD4+ T cells- help B cells make antibodies and produce cytokines to recruit phagocytes and activate other leukocytes
CD8+ T cells- kill virus-infected cells
Delayed cell-mediated hypersensitivity
Acute and chronic cellular organ rejection
45
Helper T cell + IL-12
Th1 cell
46
Helper T cell + IL- 4
Th2 cell
47
Helper T cell + TGF B + IL-6
Th17 cell
48
Positive selection
Thymic CORTEX
T cell expressing TCRs capable of binding self-MHC on cortical epithelial cells survive (enough, but not too much)
49
Negative selection
Thymic MEDULLA
T cells expressing TCTs with high affinity for self-antigens undergo apoptosis
Tissue-restricted self-antigens are expressed in the thymus due to the action of autoimmune regulator (AIRE); deficiency leads to autoimmune polyendocrine syndrome-1
50
Th1 cells
Th1 cells- secrete IFN gamma
Activates Mphages and cytotoxic T cells
Differentiation induced by IFN-gamma and IL-12
Inhibited by IL-4 and IL-10 (from Th2 cells)
Cyclical interaction between Mphages and Th1: Mphages release IL-12 --> stimulates Th1 cell differentiation --> release IFN-gamma --> stimulates Mphages
51
Th2 cells
Secretes IL-4, IL-5, IL-10, and IL13
Recruits eosinophils for parasite defense and promotes IgE production by B cells
Differentiation induced by IL-4
Inhibited by IFN gamma (from Th1 cells)
52
Helper T cells and APCs
CD4 on Th cells bind to MHC Class II of APCs
53
Cytotoxic T cells
Kill virus-infected, neoplastic, and donor graft cells (induce apoptosis)
Release cystic granules containing preformed proteins (granzymes, perforins)
54
Regulatory T cells
Help maintain specific immune tolerance by suppressing CD4 and CD8 activity
Identified by expression of CD3, CD4, CD25, and FOXP3
Produce IL-10 and TGF B (anti-inflammatory cytokines)
55
(Naive) T cell activation
1. Dendritic cell samples and processes antigen
2. Dendritic cell moves to lymph node (paracortex)
3. Dendritic cell presents antigen on MHC Class I and Class II
4. Two signals required for T-cell activation:
(a) Signal 1: Exogenous antigen (on MHC Class II) is presented by APC (dendritic cell) and recognized by TCR on CD4 T helper cell; similarly endogenous antigen (on MHC Class I ) is presented by APC and recognized by TCR on CD8 cytotoxic T cell
(b) Signal 2: Proliferation and survival; co-stimulatory signal via B7 proteins (on APC) and CD28 (on naive T cell)
5. Th cell activates and produces cytokines, while Tc cell activates is able to recognize and kill virus-infected cell
56
B-cell activation and class switching
1. Th cells are activated (using the aforementioned process)
2. B-cell receptor mediated endocytosis; B-cell presents antigen (on MHC Class II), and it is recognized by TCR on Th cell
3. CD40 receptor on B cell then binds to CD40L (ligand) on Th cell
4. Th cell secretes cytokines that determine Ig class-switching of B cell
4. B cell activates and undergoes class switching, affinity maturation, and antibody production
57
Type of antigen presenting cells
Dendritic cells (include Langerhan cells- dendritic cells of the skin)
Mphages
B lymphocytes
58
Antibody structure and function
Fab- antigen binding; consists of variable and hyper variable regions (light chain and heavy chain)
Fc- macrophage binding; complement binding (specifically IgM and IgG)
59
Antibody diversity
Antigen independent
Random recombination of VJ (light chain) or VDJ (heavy chain)
Random addition of nucleotides to DNA during recombination (by TdT- terminal deoxynuclotidyl transferase)
Random combo of heavy chains with light chains
60
Antibody specificity
Somatic hypermutation and affinity maturation (variable region)
Isotype switching (constant region)- B changes from producing one type of Ig to another (e.g. IgM to IgG
61
Naive B cells (mature)
Express IgM and IgD
Isotype switching (mediated by cytokines and CD40L)- differentiate in germinal centers of lymph nodes from B cells into plasma cells that then secrete IgG, IgE, and IgA
62
IgG
Main antibody in secondary (delayed response) to an antigen
Most abundant isotype IN SERUM (IgA is most produced, but not in serum)
Fixes complement, crosses the placenta, opsonizes bacteria, and neutralizes bacterial toxins and viruses
63
IgA
Prevents attachment of bacteria and viruses to mucous membranes
Monomer in circulation or dimer (with J chain when secreted)
Produced in GI tract (Peyer patches), and protects against gut infections (e.g. Giardia)
Released in secretions (tears, saliva, and mucus) and breast milk
Picks up secretory component from epithelial cells (protects Fc portion from proteases)
64
IgA deficiency
associated recurrent upper and lower respiratory infections and GI infections
65
IgM
Produced in the immediate response to an antigen
Fixes complement; does not cross placenta
Pentamer with J chain when secreted (valence 10)
66
IgD
Unclear, found on surface of B cells
67
IgE
Binds MAST CELLS and BASOPHILS; Cross lines when expose to allergen, mediating immediate (type I) HS through release of inflammatory mediators (such as histamine)
Mediates immunity to worms by activating EOSINOPHILS; antibody-depended, cell-mediated cytotoxicity (parasite invades and gets coated with IgG and IgE --> eosinophils then bind to Fc portion of IgE --> causes degranulation of eosinophil --> release major basic protein --> kills parasite
68
Memory cells
Antigens lacking a peptide component (e.g. LPS- lipopolysaccharides) are poorly immunogenic
Antigens with a peptide component (e.g. diphtheria vaccine) undergoes class switching and immunologic memory can occur as a result of direct contact of B cells with Th cells (CD40-CD40L interaction)
