Immunopathology: Normal Immune Function

Question 1

What is immunity?

Answer 1

Immunity is resistance (defense mechanism) exhibited by host against invasion by any foreign antigen, including microorganisms.

Question 2

What are the two types of immunity?

Answer 2

innate and adaptive immunity

Question 3

What is innate immunity?

Answer 3

Innate (Natural/Native) Immunity

• First line of defense present by birth.
• Provides immediate initial protection against an invading pathogen.
• Does not depend on the prior contact with foreign antigen or microbes.
• Lacks specificity, but highly effective. No memory, and no self/non-self recognition.
• Triggers the adaptive immune response.
• No memory is seen

Question 4

What are components of innate immunity?

Answer 4

Major Components
1. Physical/anatomical barriers: It includes epithelium lining skin, gastrointestinal and respiratory tracts act as mechanical barriers, produce anti-microbial molecules such as defensins.

2. Cells:
   Phagocytic cells: It consists of mainly monocytes (macrophages in tissue) and neutrophils in the blood. Phagocytic cells use several receptors to sense microbes and are called as “microbial sensors” (pattern recognition receptors).

Dendritic cells: These cells function as antigen presenting cells to T cells. They produce type I interferons (IFN) (e.g. IFN-), which inhibit viral infection and replication.

c. Natural killer (NK) cells: They provide defense against many viral infections and other intracellular pathogens.

3. Soluble molecules in the blood and tissues:
   a. Complement system
   b. Proteins that coat microbes and aid in phagocytosis: e.g., mannose-binding lectin and C-reactive protein.

Question 5

What is Adaptive Immunity (general features)

Answer 5

If the innate immune system fails to provide effective protection against invading microbes, the adaptive immune system is activated.

General Features
* Second line of defense acquired during life
* Capable of recognizing both microbial and nonmicrobial substances
* Takes more time to develop and is more powerful than innate immunity
* Long-lasting protection
* Prior exposure to antigen is present

Question 5

What are 3 characteristic features of adaptive immunity?

Answer 5

1) specificity, 2) diversity and 3) memory

Question 6

What are the components/types of adaptive immunity?

Answer 6

1. Humoral immunity: B lymphocytes and their soluble protein products called antibodies and helper T cells.
2. Cellular immunity: T lymphocytes and their soluble products called cytokines.

Question 7

What is the Anatomical basis of immune system – The Mononuclear-Phagocyte System?

Answer 7

Mucosa-associated lymphoid tissue (MALT)
Spleen
Lymph nodes
Thymus
Liver
Bone marrow

Question 8

Cellular operatives of the immune system

Answer 8

Lymphocytes
Macrophages
Dendritic cells
Langerhan’s cells
Interdigitating reticulum cells

Question 9

T-lymphocytes

Answer 9

60-80% of circulating lymphocytes; life span up to 10yrs
Maturation in thymus
Seen in paracortex of lymph nodes and around central arteriole of spleen
All carry the CD3 molecule on their membranes
70% are CD4 +ve: T-helper cells
30% are CD8 +ve: T-suppressor cells

Question 10

B-lymphocytes

Answer 10

10-20% of circulating lymphocytes; life span few weeks to several months
Maturation in bone marrow
Form follicles in lymph nodes, spleen (white pulp), and MALT
Marked by CD19, CD 20 and CD21
Produce antibodies after maturation to plasma cells
Stimulus for transformation is an antigenic encounter

Question 11

Natural killer cells

Answer 11

10-15% of circulating lymphocytes; non T- non B-cells hence called “null cells”
Able to destroy tumour cells as well as virus-infected cells without previous sensitisation, hence also called “natural killer cells”
Marked by CD16 molecule on their membranes
Participate in antibody-dependent cell-mediated cytotoxicity

Question 11

Macrophages

Answer 11

Found in blood and all tissues
Role in inflammation:
Phagocytosis
Release of pro-inflammatory cytokines (IL-1, TNF-alpha
Role in immune system:
Trap soluble antigens, process, and present them to T-lymphocytes
Effector cells in delayed hypersensitivity reaction; non-specific killing of tumour cells

Question 12

What are dentritic, langerhans and interdigitating reticulum cells?

Answer 12

Dendritic cells: Found in germinal centres of lymphoid follicles: present antigens to B-cells

Langerhan’s cells: Found in skin; present antigens to T-cells

Interdigitating reticulum cells: Located in paracortex of lymph nodes; present antigens to B-cells

Question 13

T-cell functions

Answer 13

Destruction of intracellular pathogens
Regulation of immune function:
T helper cells stimulate B-cells
T suppressor cells down-regulate immune response
Rejection of allograft
Destruction of malignant cells

Question 14

Activities of activated T-cells

Answer 14

Synthesis and release of IL-2, IL-4, IL-5, IL-10, and IFN-gamma
Activation of B-cells (antibody production), mast cells, and eosinophils
Direct cell killing by T-suppressor cells
Selective proliferation of a clone of antibody-producing cells mediated by T-helper cells
B-cell proliferation, which is independent of T-helper cells. These are due to certain thymus-independent antigens (e.g. pneumococcal polysaccharide, bacterial lipopolysaccharide, and dextran

Question 15

Interleukins

Answer 15

IL-2, IL-4, IL-6, and IL-9: Stimulate the proliferation, functional differentiation and activation of T-lymphocytes themselves
IL-5: Stimulates eosinophilic function against parasites and induces production of IgA and IgM
IL-10 and IL-13: Down-regulate formation of pro-inflammatory substances and switch on production of IgE and IgG.
IL-12: Induces cytotoxic activity among T-cells and NK-cells
IL-14: Induces proliferation of B-cells

Question 16

Cytotoxins: TNF-alpha
TNF-beta

Answer 16

Cytotoxins: TNF-alpha
A pyrogen
Activates clotting system and NO production
Induces synthesis of acute phase proteins
Pro-inflammatory activity by up-regulating expression of endothelial adhesion molecules
Aids in killing of Leishmania and Mycobacterium tuberculosis
Responsible for cachexia in patients with chronic diseases and cancer
TNF-beta: Share some of the pro-inflammatory effects of TNF-; strong tumour-lysing capacity

Question 17

IFN-gamma

Answer 17

Helps in defence against viral infections
Aids antigen presentation by improving the display of MHC class I and II proteins
Potent macrophage-arming factor
Helps in inflammatory reaction by up-regulating the expression of adhesion molecules on vascular endothelium

Question 18

IgG, IgA, IgM, IgE and IgD

Answer 18

IgG: Most abundant Ig (70-80%). Can neutralise toxins and opsonise bacteria. Can cross placenta and thus plays a role in intra-uterine foetal defence

IgA: Found in mucosa of GIT and respiratory tract, tears, sweat, bile and breast milk. Coats bacteria and viruses and inhibits their binding to mucosa

IgM: First antigen to be formed in infection or immunisation. IgG formation follows after the level of IgM starts to fall

IgD: Found freely in plasma and on the surfaces of B-cells. Assist the B-cell with antigen receptors for the control of their activation and suppression

IgE: Found in sizeable amounts bound to the surfaces of mast cells. On binding to appropriate antigen, cause release of histamines and leukotrienes, which initiate inflammatory reactions. Implicated in the pathogenesis of allergy

Question 19

Functions of antibodies

Answer 19

Agglutination and lysis of bacteria
Opsonisation of pathogens
Assisting with acute inflammation by fixing and activation of compliment cascade and the degranulation of mast cells to release histamine
Blocking the entry of organisms to mucosal surface and cells

Question 20

Antigens

Answer 20

An antigen is a substance that is capable of inducing an immune reaction against itself

Endogenous antigens: Found in the body:
Autologous: Normal body constituents and are recognised as self (immune tolerance) and are unique to the individual bearing them
Homologous: Found in members of the same species e.g. ABO blood group antigens and histocompatibility antigens
Heterologous: Shared by organisms that belong to entirely different species and these may be completely unrelated phylogenetically

Exogenous antigens: Found in the environment

Question 21

Histocompatibility antigens

Answer 21

The antigens are known as Human Leukocyte antigens (HLA).
This molecule is coded for by the gene cluster known as Major Histo-compatibility Complex (MHC)

Question 22

What are Class I molecules?

Answer 22

Class I molecules: Coded by the gene loci – HLA-A, HLA-B, and HLA-C. Normally displayed on the membranes of all nucleated cells and platelets. When cells are infected with viruses, their Class I molecules bind the virally-derived antigens and in this way the infected cells are recognised by CD8 cells and are destroyed

Question 23

What are Class II molecules?

Answer 23

Class II molecules: Coded by the HLA-D region. Class II molecules are normally found on the membrane of B-lymphocytes, macrophages, monocytes, and all the other antigen presenting cells