Introduction to Immunology

Question 1

Innate vs Adaptive Immunity

Answer 1

Innate:
Primary line of defence
immediate response
recognises certain threats
no antigen presentation
no clonal selection
no immunological memory

Adaptive:
Secondary line of defence
Delayed response
Recognises all threats
Antigen presentation
Clonal selection
Immunulogical memory

Question 2

State four functions of innate immunity

Answer 2

Form physical barriers - skin, mucus, cilia, commensals

Form biochemically unfavourable environments - sweat, lysozyme, gastric acidity

Phagocytosis of invading organisms - macrophages, monocytes

Destruction of extracellular parasites - eosinophils

Question 3

Name 5 sites of lymphoid tissue

Answer 3

MALT: adenoids, tonsils
Thymus: Tcell maturation
BALT: macrophages
lymph nodes: peripheral lymphoid tissue
Kupffer cells: macrophages in liver
Spleen: secondary lymphoid organ,
GALT: Peyers patches in ileum, appendix
BM: haematopoeisis, B-cell maturation
SALT: dendritic cells, macrophages

Question 4

What are the humoural components of the immune system?

Answer 4

Acute phase proteins

Lectin

Complement

Antibodies

Cytokines

Question 5

Describe the interactions between T-cells and their target cells

Answer 5

T_H cells help generate the immune response by binding to MHC Class II on antigen presenting cells. T_H1 cells help stimulate the immune response by activating macrophages which release inflammatory cytokines. T_H2 cells actiate B cells which differentiate into plasma cells and release antibodies.

T_C cells generate a cytotoxic response by binding to MHC Class I on infected cells and inducing apoptosis

Treg cells interact with Tc cells to modulate the immune system. Also involved in immune tolerance to self-antigens and are thought to be involved in autoimmune disesase

Question 6

Which 3 leukocytes are granulocytes?

Answer 6

Neutrophils
Eosinophils
Basophils

Question 7

Name 5 different types of lymphocytes

Answer 7

NK cells

Treg

T-helper

T-cytotoxic

B-cell

Question 8

What are the four main types of humoural factor in the immune system?

Answer 8

Acute phase proteins

Complement

Antibodies

Cytokines

Question 9

Give four examples of iatrogenic causes of compromised barrier immunity

Answer 9

Injection

Catheter

Mechanical ventilator

Antibiotics

Cannula

Question 10

Describe the process of phagocytosis

Answer 10

Chemotaxix and adherence of microbe to phagocyte

Ingestion of microbe by phagocyte

Formation of a phagosome

Fusion of the phagosome with a lysozome

ROS and enzymes digest ingested microbe

Formation of residual body containing indigestible material

Discharge of waste materials

Question 11

Describe the function of NK cells

Answer 11

NK cells are lymphocytes that function in the innate immune response. Capable of direct and antibody-dependent cellular cytotoxicity.

NK cells are activated through a lack of stimulation of inhibitor receptors.

Normally all human cells express MHC Class I on their surface, however this is downregulated in virus-infected and malignant cells. Lack of MHC Class I on the cell surface activates the NK cell which releases perforin onto the target cell membrane and releases cytotoxic chemicals

Question 12

What are PAMPs? Give 3 examples

Answer 12

Pathogen associated molecular patterns.

LPS, Flagellin, bacterial DNA

Question 13

Describe the complement cascade

Answer 13

The complement cascade is activated through three distinct pathways: classical, alternative and MBL.

The classical pathway is triggered by Ag-Ab complex binding to C1, or by direct binding of C1 to the pathogen surface.

The MB-lectin pathway, is triggered by mannan-binding lectin, a normal serum constituent that binds some encapsulated bacteria

The alternative pathway, which is triggered when C3 binds directly to pathogen surfaces

All three pathways result in the cleavage of C3 and C5 which result in inflammation, opsonisation of pathogens and the formation of the MAC which causes cell lysis.

Question 14

Describe the function of MHC

Answer 14

MHC proteins present antigens on the cell surface which are recognised by T-cells.

MHC Class I are present on all cell types and present endogenous (intracellular) antigens e.g. viral peptides, neoplastic antigens to CTLs

MHC Class II are only found on APCs and present exogenous antigen (e.g. engulfed material) to Th cells

Question 15

Describe antigen presentation in MHC I and MHC II molecules

Answer 15

Presentation of endogenous antigen:
Cytosolic proteins are digested by proteosomes into small amino acids. These are taken up into the ER via the TAP transporter where they are cleaved and loaded onto an MHC Class I molecule. The mature MHC I molecule is transported to the cell surface

Presentation of exogenous antigen:
External material are internalised by APCs via phagocytosis and digested in phagolysosomes. MHC Class II molecules which are made in the ER are transported to the cytosol where they are loaded with antigenic peptides and transported to the cell surface.

Question 16

Describe the components of adaptive cell mediated immunity

Answer 16

Adaptive cell-mediated immune responses involve the destruction of infected cells by cytotoxic T cells, or the destruction of intracellular pathogens by macrophages activated by TH1 cells. Mainly directed at intracellular pathogens.

Cytotoxic activity of CTLs requires recognition of antigen on MHC Class I of the infected cell and a simultaneous co-stimulatory signal from and APC (e.g. dendritic cell)

Activation causes clonal expansion and differentiation of the CTL cells. This effector T-cell progeny can act on any target cell that displays antigen on its surface.

Memory Tcells maintain immunological memory of the antigen

Question 17

Describe the process of adaptive humoural immunity

Answer 17

The humoral immune response is mediated by antibody molecules that are secreted by plasma cells.

Antigen on APCs binds to the BCR which signals B cells and is then internalized and processed into peptides that activate Th cells.

Signals from the bound antigen and Th cell induce the B cell proliferation and differentiation into a plasma cell secreting specific antibody.

These antibodies cause opsonisation, neutralisation and complement activation.

B memory cells maintain immunological memory

Question 18

Describe the process of inflammation in response to infection

Answer 18

Macrophages are activated by the presence of bacteria in the tissue or via IFNg release from active NK cells.

Activated macrophages are triggered to release cytokines that increase the permeability of blood vessels, allowing fluid and proteins to pass into the tissues and produce chemokines that direct the migration of neutrophils to the site of infection.

Endothelial cells of the blood vessels express adhesion molecules which allow neutrophils and monocytes to migrate through the blood vessel walls.

The accumulation of fluid and cells at the site of infection causes the redness, swelling, heat, and pain, known collectively as inflammation.

Question 19

Describe the process of clonal selection

Answer 19

Each lymphocyte bears a single type of receptor with a unique specificity. Lymphocytes bearing receptors for ubiquitous self molecules are deleted an an early stage in lymphoid cell development

Interaction between a foreign molecule and a lymphocyte receptor with high affinity leads to lymphocyte activation

The differentiated effector cells derived from an activated lymphocyte has receptors identical to those of the original cell.

Question 20

Decribe the role of cytokines in the immune response

Answer 20

Cytokines are small polypeptides released by a cell in response to an activating stimulus that change the behaviour of the cell.

Interleukins: They can be pro-inflammatory ot anti-inflammatory.

Chemokines: chemoattractant molecules that guide cells involved in the innate and adaptive immune response from the blood into the tissues

Question 21

Immune memory

Answer 21

Immune memory is sustained by long-lived antigen-specific lymphocytes that were induced by the original exposure and that persist until a second encounter with the pathogen.

Presence of memory cells meand that the immune response produced on the second encounter is more rapid and specific to the pathogen.

Question 22

Immune tolerance

Answer 22

Immune tolerance results from clonal deletion of lymphocytes that recognise ubiquitous self antigen and clonal inactivation by tissue-specific antigens presented in the absence of co-stimulatory signals.

This prevents auto-immune responses

Question 23

Give three histological features of chronic inflammation

Answer 23

Infiltration with mononuclear cells (macrophages, lymphocytes)

Tissue damage/destruction

Repair with angiogenesis and fibrosis

Question 24

Features of acute vs. chronic inflammation

Answer 24

Acute:
Immediate response to tissue injury
Rapid
Innate IR
Neutrophil
Hours/weeks
Prominent vascular response

Chronic:
Persistent reaction to inflammation or injury
slow response
adaptive IR
Lymphocytes and macrophages
Weeks, months, years

Question 25

Eosinophils

Answer 25

Target multicellular parasites (e.g. helminths) by releasing toxic granules (leukotrienes and peroxidases).

Specific granules target parasites while primary granules alter the airway and vasculature. This plays a role in allergic diseae e.g. asthma

Question 26

Mast cells and Basophils

Answer 26

Release histamine and pro-inflammatory mediators. Involved in the allergic response.

Question 27

What is barrier immunity?

Answer 27

Non-immunological host defence mechanisms that prevent infectious agents from entering the body.

Physical barriers: Skin, mucus, cilia, commensal organisms

Biochemical barriers: lysozyme, spermine, gastric acidity

Question 28

Name three phagocytic cells

Answer 28

Neutrophils

Monocytes

Macrophages

Question 29

What is the function of acute phase proteins?

Answer 29

Acute phase proteins rapidly increase in concentration during inflammation.

Mediate rapid, non-specific cytotoxicity and have pro-coagulant effect.

Useful biomarkers of inflammation

Include: CRP, Alk Phos, Ferritin

Question 30

Interferons

Answer 30

Proteins produced by virus infected cells (IFNa, IFNb) and Th cells and NK cells (IFNg) which inhibit viral replication and cause cell cytotoxicity.