zimmunology Flashcards
1
Q
Lymph node
A
- a 2’ lymphoid organ that has many afferents, 1 or more efferents.
- encapsulated, with trabeculae
- functions are nonspecific filtration by macrophages, storage, activation of B & T cells, antibody production
2
Q
Follicle
A
- site of B cell localization and proliferation
- in outer cortex
- 1’ follicles are dense and dormant
- 2’ follicles have pale central germinall centers and are active
3
Q
medulla
A
- consists of medullary cords (closely packed lymphocytes and plasma cells) and meduallary sinuses
- medullary sinuses communicate with efferent lymphatics and contain reticular cells and macrophages
4
Q
paracortex
A
houses T cells
- region of cortex btw follicles and medulla
- contains high endothelial venules through which T and B cells enter from blood
- In an extreme cellular immune response, paracortex becomes greatly enlarged
- not well developed in pts with DiGeorge syndrome
- paracortex enlarges in an extreme cellular immune re5sponse
5
Q
lymph drainage: area of body & 1’ lumph node drainage site
- upper limb, lateral breast
- stomach
- duodenum, jejunum
- sigmoid colon
- rectum (lower portion) of anal canal (above pectinate line)
- anal canal (below pectinate line)
- testes
- scrotum
- thigh (superficial)
- lateral side of dorsum of foot
A
- axillary
- celiac
- superior mesenteric
- colic–>inferior mesenteric
- internal iliac
- superficial inguinal
- superficial & deep plexuses–>para-aortic
- superficial inguinal
- superficial inguinal
- popliteal
* **right lymphatic duct–drains right arm, right chest, right half of head, thoracic duct drains everything else
6
Q
sinusoids of spleen
A
- long vascular channels in red pulp with fenestrated “barrel hoop” basement membrane
- macrophages found nearby
- T cells are found in periarterial lymphatic sheath (PALS) w/in white pulp of the spleen
- B cells found in follicles w/in white pulp of spleen
- macrophages in spleen remove encapsulated bact
- splenic dysfunction: dec IgM–>dec complement activation–>dec C3b opsonization–>inc susceptibility to encapsulated organisms:
1. streptococcus pneumoniae
2. Haemophilus influenzae type B
3. Neisseria meningitidis
4. Salmonella
5. Klebsiella pneumoniae
6. group B streptococci (SHiN SKiS) - postplencectomy:
1. Howell-JOlly bodies (nuclear remnants)
2. target cells
3. thrombocytosis
7
Q
thymus
A
- site of T cell differentiation and maturation
- encapsulated
- from epithelial of 3rd branchial puches
- lymphocytes of mesenchymal origin
- cortex is dense with immature T cells; medulla is pale with mature T cells and epithelial reticualr cells containing Hassal’s corpuscles
- positive selection (MHC restriction) occurs in the cortex and negative selection (nonreactive to self) occurs in the medulla
- T cells=thymus
- Bcell=bone marrow
8
Q
innate vs adaptive immunity
A
innate
- receptors that recognize pathogens are germline encoded
- response to pathogens is fast and nonspecific
- no memory
- consists of neutrophils, macrophages, dendritic cells, natural killer cells (lymphoid origin) and complement
adaptive:
- receptors that recognize pathogens undergo V(D)J recombination during lymphocyte development
- response is slow on first exposure, but memory response is faster and more robust
- consists of T cells, B cells, and circulating antibody
9
Q
What is MHC
A
-major histocompatibility complex, encoded by human leukocyte antigen (HLA) genes; present antigen fragments to T cells and bind TCR
10
Q
MHCI
A
- HLA-A, HLA-B, HLA-C
- binds TCR and CD8
- expressed on all nucleated cells. not expressed on RBC
- antigen is loaded in RER with mostly intracellular peptides
- mediates viral immunity
- pairs with beta2-microglobulin (aids in transport to cell surface)
11
Q
MHC-II
A
HLA_DR, HLA-DP, HLA-DQ
- binds TCR and CD4
- expressed only on antigen-presenting cells (APCs)
- antigen is loaded following release of invariant chain in an acidified endosome
12
Q
HLA subtype associated with dz:
- A3
- B27
- DQ2/DQ8
- DR2
- DR3
- DR4
- DR5
A
- hemochromatosis
- psoriasis, Ankylosing spondylitis, inflammatory bowel dz, Reiter’s syndrome (PAIR)
- celiac dz
- multiple sclerosis, hay fever, SLE, Goodpasture’s
- diabetes mellitus type 1, Graves’ disease
- Rheumatoid arthritis, diabetes mellitus type 1
- pernicious anemia–>B12 deficiency, Hashimoto’s thyroiditis
13
Q
natural killer cells
A
- use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells
- only lymphocyte member of innate immune system
- activity enhanced by IL-2, IL-12, IFN-beta, IFN-alpha
- induced to kill when exposed to a nonspecific activation signal on target cell and/or to an absence of class I MHC on target cell surface
14
Q
B cell functions
A
- make antibody–opsonize bact, neutralize viruses (IgG)
- activate complement (IgM, IgG)
- sensitize mast cells (IgE)
- allergy (type I hypersensitivity): IgE
- cytotoxic (type II) and immune complex (type III) hypersensitivity: IgG
- hyperacute and humorally mediated acute and chronic organ rejection
15
Q
T cell functions
A
- CD4+ T cells help B cells make antibody and produce cytokines to activate other cells of immune system
- CD8+ T cells kill virus-infected cells directly
- delayed cell-mediated hypersensitivity (type IV)
- acute and chronic cellular organ rejection
16
Q
Differentiation of T cells:
- positive selection
- negative selection
A
- thymic cortex. T cells expressing TCRs capable of binding surface self MHC molecules survive
- Medulla. T cells expressing TCRs with high affinity for self antigens undergo apoptosis
17
Q
T & B cell activation
A
- antigen-presenting cells (APCs)
- dendritic cells (only APC that can activate naive T cell)
- macrophage
- B cell
- two signals are required for T cell activation and B cell activation and class switching
18
Q
naive T cell activation
A
- foreign body is phagocytosed by dendritic cell
- foreign antigen is presented on MHC II and recognized by TCR on Th (helper) cell. Antigen is presented on MHC I to Tc (cytotoxic) cells (signal 1)
- Costimulatory signal is given by interaction of B7 and CD28 (signal 2)
- Th cell activates and produces cytokines. Tc cell activates and is able to recognize and kill virus-infected cell
19
Q
B cell activation and class switching
A
- Helper T cell activation as above
- B cell receptor-mediated endocytosis; foreign antigen is presented on MHC II and recognized by TCR on Th cell (signal 1)
- CD40 receptor on B cell binds CD40 ligand on Th cell (signal 2)
- Th cell secreted cytokines that determine Ig class switching of B cell. B cell activates and undergoes class switching, affinity maturation, and antibody production
20
Q
Helper T cells: Th1 cell vs. Th2 cells
A
Th1 cell
- secretes IFN-gamma
- activates macrophages
- inhibited by IL-4, IL-10 (from Th2 cell)
Th2 cell
- secretes IL-4, IL-5, IL-10, IL-13
- recruits eosinophils for parasite defense and promotes IgE production by B cells
- inhibited by IFN-gamma (from Th1 cell)
- macrophage-lymphocyte interaction–activated lymphocytes (release IFN-gamma) and macrophages (release IL-1, TNF-alpha) stimulate one another
- helper T cells have CD4, which binds to MHC II and APCs
21
Q
cytotoxic T cells
A
- kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis
- release cytotoxic granules containing preformed proteins
- perforin–helps to deliver the content of granules into target cell;
- granzyme–a serine protease, activates apoptosis inside target cell
- granulysin–antimicrobial, induces apoptosis
- cytotoxic T cells have CD8, which binds to MHC I on virus-infected cells
22
Q
regulatory T cells
A
- help maintain specific immune tolerance by suppressing CD4 & CD8 T cell effector function
- express CD3, CD4, CD25 (alpha chain of IL-2 receptor) cell surface markers
- activated regulatory T cells produce anti-inflammatory cytokines like IL-10 and TGF-beta
23
Q
antibody structure and function:
A
- variable part of L & H chains recognizes antigens
- Fc portion of IgM & IgG fixes complement
- heavy chain contributes to Fc & Fab fractions
- light chain contributes only to Fab fraction
24
Q
Fab antibody region
A
- antigen-binding fragment
- determines idiotype: unique antigen-binding pocket; only 1 antigenic specificity expressed per B cell
25
Q
Fc antibody region
A
- constant
- carboxy terminal
- complement binding at CH2 (IgG + IgM only)
- carbohydrate side chains
- determine isotype (IgM, IgD, etc)
26
Q
antibody diversity is generated by:
A
- random recombination of VJ (light chain) or V(D)J (heavy chain) genes
- random combination of heavy chains with light chains
- somatic hypermutation (following antigen stimulation)
- addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase
27
Q
immunoglobulin isotypes
A
- mature B lymphocytes express IgM & IgD on their surfaces
- they may differentiate by isotype switching (gene rearrangement; mediated by cytokines and CD40 ligand) into plasma cells that secretes IgA, IgE, IgG
28
Q
IgG isotype
A
- main antibody in 2’ (delayed) response to an antigen
- most abundant isotype
- fixes complement, crosses placenta (provides infants with passive immunity), opsonization bact, neutralizes bact toxins and viruses
29
Q
IgA
A
- prevents attachment of bact & viruses to mucous membrane
- does not fix complement
- monomer (in circulation) or dimer (when secreted)
- crosses epithelial cells by transcytosis
- found in secretion—tears, saliva, mucus, and early breast milk (colostrum)
- picks up secretory component from epithelial cells before secretion
30
Q
IgM
A
- produced in the 1’ (immediate) response to an antigen
- fixes complement but does not cross the placenta
- antigen receptor on the surface of B cells
- monomer on B cell or pentamer
- shape of pentamer allows it to efficiently trap free antigens out of tissue while humoral response evolves
