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MB4030 > Adaptive Immunity > Flashcards

Adaptive Immunity Flashcards

1
Q

Give examples of cell migration?

A
  • to sites of infection and inflammation
  • from blood to lymph and vice versa
  • primary to secondary lymphoid organs
  • between secondary lymphoid organs
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2
Q

Chemotaxis

A

the directional migration of cells up a conc gradient (0.1%) of chemotactic molecules

e.g. cytokine/chemokine (IL-8)
-> produced by macrophages and attracts NFs to site of infection

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3
Q

Chemokines

A
  • family of secreted chemoattractant cytokines
  • play a vital role in the cell migration between immune organs and sites of infection and inflammation
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4
Q

Number of chemokines and receptors

A

47 known chemokines
19 chemokine receptors

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5
Q

2 main groups of chemokines

A

alpha (CXC)
beta (CC)

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6
Q

Example of chemokine

A
  • IL-8 (CXCL7)
  • cells expressing CCR7 migrate to lymph nodes in response to secretion of their ligands CCL19 and CCL21
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7
Q

What are the 3 components of an inflammatory response?

A
  1. Blood supply - increased in area
  2. Capillary permeability - increased allowing exudation of serum proteins around surrounding tissue (Abs, complement)
  3. Leukocyte migration to site - phased
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8
Q

Explain the phasing of leukocyte migration as part of an inflammatory response?

A
  1. NFs - peaks 1 to 2 days (x10 increase in production in bone marrow)
  2. APCs - present at start, migrate to lymph nodes/spleen to act as APCs
  3. CTLs and Th2 - days later - must be activated by APCs in lymph nodes/spleen
  4. B lymphocytes - small numbers - secretes Abs
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9
Q

Where do chemokines bind?

A
  • secreted chemokines bind to both the proteoglycan on surface of endo cell and to the chemokine receptors on leukocytes
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10
Q

Specific Immunity

A

aka. Adaptive

Identifies each specific pathogen
e.g. H1N1 vs H5N1 influenza A virus

-> produce unique T cell responses to each antigen individually

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11
Q

Antigens

A

What the specific immune system sees
- enormous diversity of BCRs and TCRs

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12
Q

How are antigens recognised

A

Abs on B cells
TCRs on T cells

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13
Q

What does antigenicity depend on

A

Size
Hydrophobicity
Complexity

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14
Q

Epitopes

A

Antigenic determinants
- portion of a macromolecule of infection that is detected by Ab

*more complex pathogens (fungi, bacteria) will have many antigens that can be detected by different Abs

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15
Q

Examples of epitopes

A
  1. AAs - their side chains (most antigenic)
  2. Polysaccharides/sugars
  3. Lipids/nucleic acids (least antigenic)
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16
Q

Types of epitopes

A
  1. Linear
    - formed by several adjacent AA residues (~6 AAs)
    - accessible (external surface) or inaccessible (buried in protein)
    - may only be accessible when denatured
  2. Conformational
    - formed by AAs not in a linear sequence
    - spatially juxtaposed
17
Q

What is the primary function of an antibody?

A

Binds to its antigen

18
Q

Direct and Secondary effector function of Abs

A

Direct
- neutralization of bacterial toxins & viruses -> prevents binding

Secondary
- complement activation -> lysis
- opsonisation -> pathogen gets covered in Abs -> phagocytosis

19
Q

Examples of viruses that neutralise Abs

A
  1. Rhinovirus - block attachment to cells
  2. Poliovirus - block virus from uncoating capsid
  3. Influenza A - Abs enter cell and prevent replication
20
Q

How are most bacteria killed?

A

Phagocytosis
Ab-mediated opsonisation

21
Q

Why do we need T cell Immunity?

A

Viruses are intracellular pathogens

(bacteria, fungi, viruses in bodily fluids are eliminated by phagocytes (innate) and B Cells/Abs (humoural))

22
Q

Types of viruses

A
  1. Naked - Norovirus, Poliovirus (cause lysis)
  2. Enveloped - Influenza, HIV (viral envelope proteins insert into the cell membrane of infected cell)
23
Q

How does immune system see viruses within infected cells

A

(also cancer cells)

  • proteolysis of proteins in the proteasome (cytoplasm)
  • short peptides loaded onto MHC
  • shipped through ER via TAP to external surface of cell
  • T cells only recognise peptides when bound to MHCs on APCs or infected cells

*self reactive T cells already eliminated during thymic education

24
Q

How are virus peptides on surface of infected cells seen?

A

CD8 (CTLs) w/ TCRs recognise peptide bound to MHC

NKs recognise infected cells w/ no MHC
-> apoptosis

25
Q

What bridges the innate and adaptive immune system?

A

Macrophages and DCs

26
Q

MHC classes and cell type

A

MHC I - CTL -> apoptosis
MHC II - Th cell -> cytokines secreted

27
Q

TCRs

A

Polymorphic - VDJC gene fusions in thymus

28
Q

Tri-molecular complex

A

TCR + Antigen + MHC

29
Q

TCR a and beta have a net ….. charge?

A

Positive

30
Q

CD3

A

5 proteins that are non-covalently associated with TCR

  • involved in signal transduction following antigen recognition
31
Q

MHC classes

A

MHC I - expressed on ALL nucleated cells (~10 AAs)

MHC II - expressed on APC surface
(15-25 AAs)

32
Q

Sources of peptides for MHC I vs MHC II

A

MHC I - proteosomes

MHC II - endolysosomes (peptides from pathogens that have been phagocytosed by APCs)

33
Q

Function of proteasome

A

Housekeeping function
- degrades damaged and improperly folded proteins
- recycling of old worn out proteins

34
Q

Apoptotic cell death mechanisms of virus-infected cells

A
  1. Ab (as part of ADCC)
  2. CTL recognition of virus peptides bound to MHC I on surface of infected cells
  3. NK cell recognition of loss of MHC I on surface of infected cells
  • removal of apoptotic bodies via macrophages
35
Q

How do cells kill via apoptosis

A

Perforin - polymerises and generates transmembrane pores on target cell surface

Allows other granule contents to enter their target cells
- Granzyme B
- DNAse
- Fas engagement via FasL

36
Q

Granzyme B

A

activated apoptosis by activating caspases (3) - cleaves substrates

37
Q

Explain the process of phagocytosis

A
  • phosphatidylserine residues expressed on inner plasma membrane which are redistributed onto outer surface of dying cell
  • Phagocytes have phosphatidylserine receptors
  • allows for binding, removal and destruction of apoptotic bodies
  • apoptotic bodies destroyed within phagolysosomes of phagocytes

MB4030 (11 decks)

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