CGIER 20 - Immunology

Question 1

Immunology

Answer 1

study of body’s defence mechanisms

Question 2

David Phillip Vetter - The Boy in the Bubble

Answer 2

(1971– 1984)
Severe combined immunodeficiency(SCID)
First person to live in sterile conditions
Successful bone marrow transplant
Months later became ill and died fromBurkitt’s lymphoma age 12
Bone marrow from sister contained an undetected dormant virus Epstein-Barr. Once transplanted, the virus spread and produced hundreds of cancerous tumors.

Question 3

First Line of Defence

Answer 3

• Keratin Epithelial lining of skin
• Lysozyme (in tears)
• Acidity of skin

Question 4

Second Line of Defence

Answer 4

• Inflammatory
• Pyrogens (proteins produced by cells to raise overall body temperature to limit antimicrobial growth)
• Interferons (cytokine proteins interfere with virally infected cells, mechanisms to identify self, destroy non-self, inhibit viral reproduction, e.g. interferon gamma)
• Complements (series of 20 proteins able to attach, build core hollow tube on bacterial surface, worms its way into the surface of the bacteria, cell wall becomes weak, possibility of cell lysis, cell bursts open)

Question 5

Third Line of Defence

Answer 5

• Selectively targeting foreign bodies (learned mechanisms)
• Lymphocytes adapted immune response specifically producing proteins that can bind to antigen specifically, (T cells, B cells)

Question 6

MHC Receptors

Answer 6

• Major Histocompatibility Complex, Human Leukocyte Antigen (HLA)
• Proteins for “antigen presentation” to T cells of specific immune system
• Polymorphic - each individual has a unique set of MHC proteins, causing problems in transplantation (recognized as non-self by recipient’s immune system)
• Most cells have MHCI, some have MHCII for leukocytes and macrophages

Question 7

Non-specific Immune Mechanism

Answer 7

• “Innate” / ”natural” / “native”
• Physicochemical barriers (Skin cuticle, tears, saliva, gastric juices, mucus…..)
• Innate cells: Phagocytes, platelets, natural killer cells, eosinophils, monocytes & neutrophils.
• Depends on recognising “Pathogen Associated Molecular Patterns” (PAMP)
  e.g. Bacterial polysaccharides should never be present in the body and are recognised as non-self

Question 8

Specific Immune Mechanism

Answer 8

• “Adaptive “immunity
• Complex system specifically recognizes foreign antigens, relies on antibody binding
• Has immunological ‘memory’

Question 9

Anatomical/Chemical (non-specific defence mechanism)

Answer 9

• Skin provides physical barrier against pathogens
• Secretions in sweat and sebum destroy some bacteria (e.g. anti-microbial lysozyme)
• Microorganisms entering the gut are usually destroyed by stomach acids
• Those entering the lungs are trapped by sticky mucous lining bronchi and bronchioles

Question 10

Cytokines

Answer 10

Special proteins secreted by immune system cells:
- Interferons
(released in viral infections, “warning system” effective in inhibiting viral replication and production of viral proteins, stimulate other immune responses) e.g. INF-y
- Interleukins
(secreted by macrophages and lymphocytes, regulate interactions between various parts of the immune system) e.g. IL-1, IL-2, IL-4

Question 11

Inflammation

Answer 11

Tumor (swelling) - Calor (heat) - Dolor (pain) - Rubor (redness)
- Inflammatory response mediated by various cytokines and proteins
- Damaged cells release histamine, serotonin, dilate blood vessels in infected area
- Capillary wall permeability increases, tissue oedema
- Increased blood flow allows cells/molecules of immune system to more easily reach site of injury
- Immune cells attracted to site by specific cytokines

Question 12

Pyrexia

Answer 12

Increase in body temp (fever) caused by neutrophils releasing endogenous pyrogens (IL-1, Prostaglandins)
Pyrogens reset the body;s thermostat in the hypothalamus to a higher temperature, directly affects bacterial metabolism

Question 13

Macrophages

Answer 13

• Develop from monocyte precursor cells
• Some are resident in tissues and destroy passing bacteria / damaged body cells
• Numerous in gut wall and lungs
• Others circulate in bloodstream, patrol for bacteria
• Phagocytosis
• Release cytokines, influencing the behavior of other cells

Question 14

Neutrophils

Answer 14

• Smaller
• Phagocytose 20 bacteria before dying
• Blebbed nucleus
• Most common WBC

Question 15

Specific Defence Mechanisms

Answer 15

Once activated (day or two) effective in cell-mediated immunity and antibody-mediated immunity with lymphocytes

Question 16

Cell-Mediated Immunity

Answer 16

3 cell types: T-lymphocytes, Natural Killer Cells, Macrophages
2 populations of lymphocytes both derived from the lymphoblasts in the red bone marrow: T-lymphocytes and B-lymphocytes
Before or soon after birth they migrate to various lymphatic tissues and organs in the body
T-lymphocytes undergo maturation in the thymus gland, develop “immunological competence”

Question 17

T-lymphocyte maturation

Answer 17

TCR (T-cell receptors) recognize antigens when presented in context of MHC molecule
During maturation, any T-cell with a receptor that recognises self-antigens is destroyed -> Mature T-cells only recognise foreign antigens
Mature T-cells are stored in an inactive state as “small lymphocytes”
Constant region and variable region (exact specificity), binds to antigen MHC complex, complementary binding, B cell will become activated, sets off cascade for humoral immune response

Question 18

Foreign antigen is phagocytosed by…

Answer 18

Antigen presenting cells (APC)
e.g. macrophages, neutrophils, dendritic cells
- Peptides derived from those antigens are complexed with MHC molecules and presented on the surface of the APC
- The presented antigen is recognised by a T-cell with a receptor that can bind to that antigen
- Fewer than 1 in 10,000 cells may respond

APC ingests and destroys antigen, fragments are linked with MHC molecules (MHC complex), expressed on cell membrane of APC cell

Question 19

T-cell Activation

Answer 19

Responding cell now becomes activated/sensitized -> sensitized cell increases in size, divides mitotically to form a clone of cells similar to itself -> cells differentiate into a variety of specialised cells = T-cell Subsets
= 4 cell types: cytotoxic T-cells, helper T-cells, suppressor T-cells, memory cells

1. T-cells leave the lymph nodes and migrate to the site of infection and release a variety of cytokines and cytotoxins;
2. Cytotoxic T-cells interact with cells carrying foreign antigens, releasing molecules (like perforin-1 which forms membrane pores, degrades bacteria wall) that kill the target cell
   helper T-cells perform various functions (such as: release of interleukins at the infection site and activation of antibody-producing B-cells)

All cells will undergo multiple bouts of mitosis, produce multiple T cells, exact same T cell receptor specific for interaction, activation of cytotoxic T cells

Question 20

Clonal selection

Answer 20

Produce many clones, activated
T cell produces hundreds of thousands of same cell with same receptor, some will be cytotoxic, helper, memory, suppressor

Question 21

T-cell Subsets

Answer 21

1. Cytotoxic T-lymphocytes
2. Helper T-lymphocytes
3. Suppressor T-lymphocytes
4. Memory cells

Question 22

Cytotoxic T-lymphocytes

Answer 22

recognize and destroy cells with foreign antigens
including infected body cells (viruses), bacteria, protozoa, fungi, cancer cells, organ transplants
can identify and destroy cancers

Question 23

Helper T-lymphocytes

Answer 23

enhance the immune response
60% of circulating T-cells
- T-helper 1 cells release Interleukin-2 -> stimulates other T-cells
- T-helper 2 cells release Interleukin-4 -> stimulates proliferation of B-cells

Question 24

Suppressor T-lymphocytes

Answer 24

controversial, less understood
suggested to turn off the immune response when fewer antigens present
release suppressor cytokines

Question 25

Memory Cells

Answer 25

remain in lymphatic tissue for many years
responsible for secondary immune response

Question 26

Natural Killer Cells

Answer 26

• Similar to cytotoxic T-cells
• Non-specific (do not depend on recognising and binding to foreign antigen)
• Recognise cells with altered cell-surface

Cancer cells often have unusual protein expression and their cell surface is abnormal – recognised and destroyed by NK cells

Question 27

Immune Response

Answer 27

Primary
- First exposure of body to new pathogen
- May take 3-14 days

Secondary
- Subsequent exposure to the antigen
- More rapid, dramatic reaction due to presence of memory cells bearing receptors to antigen
- Shorter latent period
- Much less antigen is required, more antibodies produced, pathogen destroyed before it can get established