Immunology

Question 1

1ary vs 2ry lymph tissues?

Answer 1

1ary: bone marrow, thymus for maturation
2ary: all other lymphoid tissue: nodes, spleen, tonsils, MALT, GALT

Question 2

Anatomy of lymph node - where are macrphoages, B, Ts

Answer 2

• medularry cords: macrophages, plasma cells
• paracortical area: T cells
• cortical area: B cells and germinal centres

Question 3

Where are we most prone to infection and what structures are there to help?

Answer 3

tracts:

1. gastrointestinal: tonsils and adenoids; peyer’s oatches, intestines have most lymphocytes in body
2. resp
3. urogenital

Question 4

Macrophages?

Answer 4

• phagocytosis!
• apc
• repair
• secrete pro-inflamm cytokines

Question 5

Neutrophil?

Answer 5

lots in blood; 1st line after epithelial/mast cells

1. phagocytosis
2. degranulation to kill
3. NETs - form net with antimicrobial peptides to kill
4. signal to recruit others

Question 6

Eosinophils?

Answer 6

• kill ab-parasites

- in allergic rxns

Question 7

Basophils?

Answer 7

• unknown
• similar to mast cells
• allergic rxns

Question 8

Mast cells?

Answer 8

• release granules iwith vasoactive amines

- anaphalyxis, type 1 hypersen

Question 9

What are TLRs?

Answer 9

toll like receptors

• pathogen-associated molecular pattern receptors on cells
• each TLR recog one type of microbial component
• can be at membrane surface or intracellular
• binding > signalling cascade > transcription factor (NF-kB) > protein production to respond > cytokines

Question 10

Dendritic cells?

Answer 10

• apc
• migrate to lymph nodes to activate lymphocytes
• link innate and adaptive

Question 11

Role of antibodies?

Answer 11

1. neutralization - binds toxin, viruses
2. opsonization
3. complement activation via classical pathway
4. activate other cells
5. RECOGNIZE specific epitopes not just patterns of antigen protein

Question 12

How is tolerance obtained?

Answer 12

• delete autoreactive T cells in thymus
• delete autoreactive B cells in bone marrow
• anergy of autoreactive cells after development
• Tregs suppressing fnc
• immunoinhibitory receptors
• presence of barriers for priveleged sites

Question 13

List components of INNATE immune system:

Answer 13

• physical barriers: skin, pH, mucus
• mast cells
• neutrophils
• macrophages
• NK cells
• dendritic cells

-non specific recognition (patterns); killing; signals for inflame; activation of adpative immune cells; no memory

Question 14

How does innate system recog pathogen?

Answer 14

1. TLR recognizing PAMP

2. inflammasome: cytoplasmic proteins send danger signal in presence of PAMPS > IL1 secretion to initiate inflamm

Question 15

linking bt innate and adaptive

Answer 15

Dendritic cells
cytokines (from macrophages)
complement cascade

Question 16

What are the chemical (non cellular) components of immune system?

Answer 16

4 C's:
Cytokines
Complements
Chemokines
Coagulation

Question 17

What is phagocytosis? Who does it?

Answer 17

-recognition: TLR, Fc, mannose, complement
-pseudopod to surround pathogen
-engulf
-phagolysosomal fusion > digestion
» also lead to antigen presentation, and cytokine release
-neutrophils, macro, B cells, dendritic cells

Question 18

How does immune system kill?

Answer 18

1. Phagocytosis
2. complement cascade
3. ADCC: antibody-dependent cell mediated cytotoxicity
   - ab opsonize for NK cells, neutrophils, eosinophils to relesase granules for killin
4. Defensins: antimicrobial from neutrophils
5. Pentraxins; link pathogen adn phagocyte

Question 19

Purpose of complements?

which one is important?

Answer 19

1. direct killing (MAC) - C5b onward
2. opsonization -C3b
3. recruiting inflammatory cells -C3a, C5a

Question 20

Role of cytokines?

ex:

Answer 20

-activate other cells
-chemotaxis
-activate liver to secrete proteins: complements, opsonization
-on bone marrow to recruit neutrophils
-on hypothalamus, fat, muscle > fever
-on dendtritic cells >migration and link adaptive response
IL1, IL6, IL12, TNFalpha

Question 21

Why is C3 impt?

Answer 21

activation of complement > C3 convertase metabolizing C3 > C3a: ENDO PERM, activation of phagocytes = inflammation
>C3b (bigger piece): opsonization with receptor for phagocytes

def: recurrent infections

Question 22

Early vs late complement cascade?

what if deficiency?

Answer 22

early: binds antigen-ab complexes > C3 activation
def > not so serious b.c of multiple pathways to C3
C4 def in SLE

late: killing via MAC (creates holes in membrane)
def > serious inf (gonorrhea, meningitis)

Question 23

Describe B cell development

Answer 23

develops in bone marrow:
>ProBcell: commits to B cell line
>preBcell receptor: heavy chain gene rearrangement. checks for functional heavey chain else apoptosis.
>light chain gene rearrangement
>Bcell receptor. checks for functional else.
=Immature B cell with IgM expression
>exposed to self-antigen. Only those that DO NOT self-recog can leave bone marrow

Home via chemokines in blood > activated when in contact with antigen > diff, proliferate, mature:
IL10 >plasma cells > goes to bone marrow > produce antibodies > IgM first then others
IL4 > Memory B cells > IgG early response next time

Question 24

Antibody structure, production, response

Answer 24

• Fc-constant for binding to receptors on phagocytes
• Fab-variable for recognition of antigen
• antibodies: opsonize, neutralize, activate complements, activate cells

Question 25

Antibody isotypes and fncs

Answer 25

IgG: in serum, tissue, cross placenta. small. opson & complement activation IgA: dimeric. in secretions (tracts!). Neutralization - bind and excrete. Week ops and activation. IgM: first response. pentameric. big so not diffused well. in circulation. CANNOT recruit other cells. activate complements IgE: trace amounts in serum. bound to mast cells under skin/mucosa > reactions to expel pathogen. -allergies, parasites IgD - didn't mention

Question 26

B cell tolerance

Answer 26

Central: - immature B cell exposed to self-antigen. If recognize self > negative signal for apoptosis = NEGATIVE SELECTION - TOLERANT B cells can leave bone marrow

Question 27

Clonal selection hypothesis?

Answer 27

-common precursor cell > remove self-reactive immature lymphocytes > antigen presence would activate proliferation of specific lymphocyte differentiation

Question 28

Describe B cell genetic Recombination

Answer 28

*must generate large repertoire of antibodies, but each must only recognize one specific antigen. < done via GENETIC RECOMBINATION > diveristy! Bone Marrow: -3 gene segments on antibody VARIABLE region rearranged and assembled: -heavy chain: random V, then random D+J added to V -light chain: kappa then lambda -Heavy and light chain combination *antigen independent Lymph node: under specific signals -isotype switching - recombination of CONSTANT genes

Question 29

Describe B cell activation in lymph nodes. | 1ary vs 1ary focus?

Answer 29

- goes to lymph node vis HEV * surface antibody-antigen binding + coreceptor binding - also helped by Thelper cells that recogn same antigen> express CD40L to CD4 on B cell + cytokine binding - PRIMARY FOCUS: clonal expansion adn IgM in medullary cords - 2ary FOCUS: B cell move to cortical area > germinal center > later better response. Needs presence of Thelper cell, follicular dendritic cells, activated B cells

Question 30

What occurs in a germinal centre?

Answer 30

-activated B cells under strong cytokine signalling and interaction with dendritic cell, antigen, Thelper > rapid proliferation -SOMATIC HYPERMUTATION occurs > B cells with higher affinity for antigen selected for = AFFINITY MATURATION -ISOTYPE SWITCHING: recombination of CONSTANT genes expressed for same V region >>swollen lymph nodes. 1 wk post infection

Question 31

T cell development

Answer 31

-Precursor formed in bone marrow > arrive thymus: VJ rearrganement of TCR + positive selection + negative selection: -Rearrange B chain - DJ then VDJ. CHECK PreT cells -proliferate as DOUBLE NEGATIVE PreTcell. CHECK -DOUBLE POSITIVE Immature T cell -Rearrage alpha chain - VJ. CHECK. Now DOUBLE POSITIVE mature T cell (have both CD4 and CD8 receptors) -positive selection- keep those that can recog self MHC and only express one CD coreceptor -negative selection-rid those that can recog self antigen - mature, self-restricted, self-tolerant, single positive NAIVE Ts migrate to 2ry lymphoid - becomes effector cells after antigen exposure > proliferation and differentiation

Question 32

CD4T vs CD8 T? | binds which MHC

Answer 32

*a:B TCRs CD4 -help other cells; extracellular pathogens -binds MHC 2 CD8 - kill cells with virus/intracellular pathogens - binds MHC1

Question 33

T cell tolerance

Answer 33

* Positive selection - can T cell bind self MHC? Yes - keep. * Negative selection - can T cell bind MHC with self antigen? Yes - RID! - test in medulla of thymus with APCs presenting peptides made by apcs, from macrophages, from extracellular fluid, and peptides of things outside thymus transcribed by AIRE gene * priveleged sites * Peripheral tolerance mechanisms: - Treg suppression of naive autoreactive cells (natural in thymus; inducible in periphery); foxp3 transcription factor - anergy of autoreactive cells

Question 34

Immunological memory?

Answer 34

-2ry immune response -B cells, T cells, antibodies of previous infection remain >faster, stronger response next time -long lived cells maintained by cytokines

Question 35

What is B-T cognate interaction?

Answer 35

-antigen recogn > induce expression of CD40L and cytokines from Th2 cells > activate B cells

Question 36

What is MHC? What is MHC Restriction? How is MHC diversity achieved?

Answer 36

- major histocompatibility complex - antigen protein needs to be fragmented and specific epitope presented on MHC for TCR to recognize - can bind many different aa sequences (motif) - T cell is specific to that antigen on that MHC * no recombination - diveristy is inherited from each parent

Question 37

MHC 1 vs 2? which cells have which? | binds to which T cells?

Answer 37

MHC I: on all nucleated cells -binds CD8T for intracellular infections MHC II: on apcs -binds CD4T for extracellular infections

Question 38

How are antigens presented?

Answer 38

-APCs take up: endocytosis or comes in -degrade: phagolysosomes or proteasomes -proteins unfolded adn cut -specific peptide bind to MHC adn brought to surface MHC II: produced and fuse with vesicle containing antigen while MHC I: have peptides brought to ER and packaged together -T cell comes by and bind...

Question 39

How are T cells activated?

Answer 39

-from APCs: dendritic cells, macrophages, B cell 1. TCR bind MHC with specific antigen 2. Co-stimulation: CD28 with CD80 (B7) ligand on APC >>gene transcription > cytokines > effects on other immune cells ex: IL2 > further proliferation of T cells >>effector T cells don't need costimulation to respond!

Question 40

What is anergy? How?

Answer 40

- T cell can't be activated - MHC and antigen signal but NO costimulation - helps to prevent activation to self-antigen

Question 41

Type of CD4 Helper T cells? | which cytokines are impt?

Answer 41

Naive CD4 T cells can differentiate to diff effectors under diff cytokines: - Th1 - activate macrophage (IFN-gamma) - Th2 - activate B cells (IL4, IL5) - Tfh - activate B cells to form germinal centre (IL21, IL4) - Th17 - enhance neutrophil response where Th1 and Th2 not enough; autoimmune. (IL17, IL6) - Treg - suppressor T (TGF-beta, IL10)

Question 42

How does TB hide from immune system?

Answer 42

- hides from lysosomal degradation > can't be presented by MHCII - does not enter cytoplasm > can't be proteasased > can't be presented by MHCI - T cells can't recognize. - T cells surround the APCs with TB = granuloma

Question 43

How does leprosy present differentially depending on host response?

Answer 43

cytokine levels > certain cell differentiation - bias toward Th1 response > cell mediated presentation: macrophages can suppress > slow > damage to skin and nerves - bias toward th2 > antibodies can't access bacteria in macrophages > bacteria grow > severe destruction!