Immunity

Question 1

What are the 5 types of while blood cells in innate immunity?

Answer 1

Macrophages
Monocytes
Basophils
Eosinophils
Neutrophils

Question 2

What are the 4 components of the Innate immune system?

Answer 2

Physical barriers – epithelial surfaces

Cellular components – phagocytes and NK cells

Complement system and mediators of inflammation

Cytokines

Question 3

How do physical barriers aid immunity?

Answer 3

Epithelial surfaces – skin, GI tract, respiratory tract, urinary tract

Secrete anti microbial substances – defensins

Epithelia also contain lymphocytes and mast cells

Question 4

What are the cellular functions that aid immunity?

Answer 4

Recognise structures on microbes using pattern recognition receptors

These result in

• phagocytosis of pathogen by macrophages or neutrophils
• killing of infected cell by NK cells
• presentation to T cells by dendritic cells

Question 5

What are lipopolysaccharides?

Answer 5

Also known as endotoxin

Product of gram negative bacteria cell wall

Stimulates innate immune system

Pathogenic- induces local and systemic inflammation

Question 6

What is phagocytosis?

Answer 6

Mediated by neutrophils and macrophages

Neutrophils most numerous wbc, 1st on scene

Microbe binds to cell surface receptors and is endocytosed

Phagosome fuses with lysosomes containing degrading
enzymes – lysozyme, collagenase & elastase plus ROIs and NO

Question 7

What are the 5 steps of phagocytosis?

Answer 7

1. Bacteria attaches to membrane
2. Bacteria is ingested, forming phagosome
3. Phagosome fuses with lysosome
4. Lysosomal enzymes digest material
5. Digestion products are released

Question 8

What are natural killer cells?

Answer 8

Appearance of large lymphocytes w/o TCR or mem bound Ig

Recognise microbial markers on surface of infected cells

Perforins make holes in membrane allow entry of granzyme

Infected cell dies by apoptosis

Question 9

What are cytokines?

Answer 9

Small proteins that control growth and activity of immune system and blood cells
Produces by T cells

Mediate many of the effector functions of innate system

Question 10

How can we reregulate cytokines to prevent disease?

Answer 10

• Mop up excess cytokines with soluble receptors
• Stimulate or block cytokine receptors
• Try to restore the homeostatic balance of pro vs anti inflammatory cytokines

Question 11

What are B cells?

Answer 11

Mature in the bone marrow and express IgD receptors on surface

Antigenic challenge (in lymph node) results in processing and presentation of antigenic fragments to Th cells

Th2 cells provide costimulatory signals required for B cell activation and ab production (CD40L and IL-4)

Some remain after antigen elimination as memory cells

Question 12

How are B cells activated?

Answer 12

activated by engagement of surface abs plus costimulatory signals from t cells, signal enhanced by engagement receptor

Question 13

How are B cells downregulated?

Answer 13

signal downregulated by engagement of Fc coreceptor

Question 14

What are antibodies?

Answer 14

Produced by B cells –humoral immunity

Represent 20% plasma protein

Specific recognition of antigen

Target circulating microbes and toxins for phagocytosis

Provide active and passive immunity

Question 15

What is the structure of antibodies?

Answer 15

Basic unit comprises two heavy chains and two light chains
(k or l) joined by disulphide bonds

Question 16

How are antibodies typed?

Answer 16

IgM - first to be produced, natural abs in peritoenum, complement activation
IgD - Naive B cell ag rec
IgA - epithelial/mucousal immunity
IgE - helminthic parasites and immediate hypersensitivity
IgG - secondary exposure, neonatal immunity, ab dep cell med cytotoxicity

Question 17

How are antibodies produced?

Answer 17

During maturation in the bone marrow B cells undergo irreversible genetic recombination to produce and antibody of restricted specificity

Question 18

What are Fc mediated effects?

Answer 18

Fc region mediates many motor functions of antibodies, variability in Ig class affects function

Question 19

What are the three ways that antibodies are used as tools?

Answer 19

• in labs to detect proteins
• detecting antibodies can be diagnostic
• prevention/treatment of disease

Question 20

What are the 2 challenges of antibody based therapies?

Answer 20

• quick to develop but expensive to produce
• proteins require injection

Question 21

What are T cells?

Answer 21

Thymus selected lymphocytes required for cell mediated immunity
Removal for intracellular pathogens by killing infected cells

Question 22

What are the two types of T cells?

Answer 22

Helper t cells - (Th1- activation, Th2 - costimulatory)
Cytotoxic T cells

Question 23

What is TCR?

Answer 23

Similar structure and assembly as antibodies

Associated with CD3 signalling chains and CD4/8

Undergo thymic selection
for self tolerance

No somatic hypermutation
– ag affinity remains low

Question 24

What is major histocompatibility complex?

Answer 24

A group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances

Question 25

What is antigen recognition?

Answer 25

T cells only recog small fragment of ag
requires endocytosis, processing and presentation by apc in conjunction with MHC molecule
peptide fragments bind in groove of MHC
TCR binds across peptide and MHC residues
CD4/8 bind MHC to prevent T cells killing apcs

Question 26

What is thymic selection?

Answer 26

Developing T cells encounter self antigen presented on self MHC found on thymic epithelial cells
If T cell does not recognise and bind MHC - signaled to die by apoptosis - positive selection
If T cell binds strongly and activation - signalled to die by apoptosis - negative selection
Surviving T cells kept alive in peripheral lymphoid organs by continual interaction with self peptide
become activated only when encountering foreign antigen presented on self MHC

Question 27

What is co-stimulation?

Answer 27

T cells do not respond to antigen alone
Normal T cells activation requires a second signal, without this, T cell is unresponsive

Question 28

What is the difference between TH1 and TH2??

Answer 28

TH1 cells
- migrate to site infection
- release IFN to activate macrophages
- stimulate production of monocytes
- increased expression of adhesion molecules
TH2 cells
- provides signal 2 to B cells

Question 29

B cells produce
T cell produce

Answer 29

B - antigen
T - cytokine

Question 30

What 4 things do mast cell mediators cause?

Answer 30

• increased vascular permeability
• vasodilation
• bronchial and smooth muscle con
• local inflammation

Question 31

What are allergens?

Answer 31

• usually requires repeated exposure before immune response
• many allergens are small, glycosylated molecules with high solubility in body fluids

Question 32

What are the three mechanisms of autoantibodies?

Answer 32

• activate complement and stimulate phagocytosis
• can recruit neutrophils which cause tissue damage
• can bind to receptor and alter function

Question 33

What are immune complexes?

Answer 33

systemic disease (lupus)
can occur after multiple injections
usually occurs in small vas beds, joints and renal glomeruli
(treated with steroidal anti-inflammatories)

Question 34

What is cell-mediated tissue injury?

Answer 34

Delayed hypersensitivity
Mediated by TH1 and CD8 cells
Release IFN to activate macrophages and TNF to induce inflammation
Tissue damage caused by hydrolytic enzymes

Question 35

What is autoimmunity?

Answer 35

-Results from failure of mechanisms for maintaining self-tolerance
- Main factors are genetic susceptibilty and environmental triggers

Question 36

Which autoimmune diseases are organ specific?

Answer 36

IDDM
MS

Question 37

How does transplantation work?

Answer 37

• immune response of recipient to donor tissue
• recognise donor MHC as foreign
• donor tissue killed by CTL, TH cells and abs
• requires blood and tissues for typing

Question 38

How is blood type decided?

Answer 38

• everyone has basic glycolipid antigen (O) and some have attached carbohydrate groups (A,B)
• Group A blood produces anti B antibodies and Group O has anti A and B antibodies

Question 39

What is the difference between acquired and congenital immunodeficiency?

Answer 39

congenital - x-linked agammaglobulinemia (eg SCID)
acquired - from infection or disease (cancer or HIV etc)

Question 40

How does HIV progress?

Answer 40

• infects dendritic cells and carried to lymph nodes
• activation of CTLs and antibody production results in partial control of infection
• infects T cells via CD4 and chemokine receptors
• gradually causes lymphpenia, patients at risk of opportunistic infections