Lecture 20 Flashcards by Shareen Arneja

What is Immunology?

-bacteria, viruses and parasites can cause disease in humans (pathogens)

All animals have internal defence mechanisms that provide protection against disease causing organisms or pathogens
-immunology is about destroying pathogens without self harm.

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The boy in the bubble

-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.

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First line of defense

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

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Second line of Defense

-Inflammatory
-Pryogens ( proteins produced by cells to raise body temp and limit mictobule growth)
-Interferons (interfere with virus infected cells)
-Complements (20 different proteins that attach like lego blocks
T cells raising proteins that kills antiogens

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Third line of defense

-Selectively target foreign bodies
-Lymhocytes (B-cells and T-cells)

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Self and non-self

The immune response is the process of the organism to distinguish between itself and foreign matter (self and non-self), responding and eliminating it

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Self and non-self

The immune system can recognise cell surface macromolecules - proteins or polysaccharides to distinguish an endothelial cell from a bacteria for example.

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MHC receptors

MHC type 2 for certain types leukocytes like macrophages and white blood cells
MHC type 1 is most cells in body

-polymorphic - each individual has a unique set of MHC protein protein: this causes problems in transplantation
-a donated organ with MHC proteins different from the recipient is recognized as non-self by the recipients immune system and attacked
-major histocompatibility complex (MCH) human leukocyte antigen (HLA) are proteins important in recognizing foreign antigens (antigen presentation to T cells of specific immune system)

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Immune mechanism (non-specific)

-physiochemical barriers (skin cuticle, tears, saliva, gastric juices, mucus)
-innate cells include; phagocytes, platelets, natural killer cells, eosinophils, monocytes &neutrophils
-depons on recognizing “Pathogen associated molecular patterns (PAMP)
-ex. bacterial polysaccharides should never be present in the body and are recognized as non-self
-can cause damage to tissue(autoimmune effect)

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Immune mechanism (specific)

-adaptive immunity
-complex system specifically recognizes foreign antigens
-relies on antibody binding
-has immunological memory

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Non specific and specific

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Non-Specific Defence Mechanisms - Anatomical/chemical

The skin provides one of the most important
defences - a physical barrier against pathogens

-produces secretions in the sweat and sebum which destroy some bacteria (e.g. Anti-microbial lysozyme);

microorganisms entering the gut destroyed by the stomach acids;

those entering the lungs are trapped by the sticky mucous lining the bronchi and bronchioles.

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Non-Specific Defence Mechanisms
Cytokines

Pathogens entering the tissues cause various cells of the immune system secrete special proteins collectively called cytokines;

Interferons – one group of cytokines released in viral infections which are effective in inhibiting viral replication and production of viral proteins; also stimulate other immune responses; e.g. INF- γ

Interleukins – secreted by macrophages and lymphocytes: regulate interactions between various parts of the immune system.
e.g. IL-1, IL-2. IL-3..
-important for wound healing

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Non-Specific Defence Mechanisms
Inflammation :

Tumor - Calor – Dolor - Rubor
Swelling Heat pain redness

The inflammatory response is mediated by various cytokines and other proteins;

damaged cells release histamine, serotonin and other substances which dilate the blood vessels in the infected area;

capillary wall permeability increases leading to tissue oedema;

the increased blood flow allows the cells and molecules of the immune system to more easily reach the site of injury/infection

immune cells are attracted to the site by specific cytokines

Lymphocytes moving to wound site

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cells of the immune system

Suffer from heart attcak, that person can be injected with stem cells
T cells move up thymus ( it matures for cells to identify self and non self)

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Non-Specific Defence Mechanisms: Inflammation

Sometimes the entire body is involved producing fever, or pyrexia;
this is thought to be caused by neutrophils releasing endogenous pyrogens, including Interleukin-1 and Prostaglandins;

Pyrogens reset the body’s thermostat in the hypothalamus to a higher temperature which directly affects bacterial metabolism.

Interleukin and prostagrandin causes temperature to increase

Bacteria can grow at 37 but when it increases to 38 it wont grow well which is why we have fevers
If we have prolonged fever it can affect and damage tissue

Inflammatory response

Non-Specific Defence Mechanisms
Phagocytosis

The main phagocytic leucocytes are macrophages and neutrophils

Macrophages

develop from precursor cells called monocytes

some are resident in tissues and destroy passing bacteria and old and damaged body cells

they are particularly numerous in the gut wall and lungs.

others circulate in the bloodstream, patrolling for bacteria

as well as carrying out phagocyotosis, they release cytokines - influencing the behaviour of other cells

Neutrophils

are smaller ; phagocytose about 20 bacteria before dying; blebbed nucleus, most common WBC

Specific Defence Mechanisms

The non-specific defence mechanisms prevent the spread of infection until the specific mechanisms can come into play;

this may take a day or two but, once activated, they are very effective and of two main types both involving lymphocytes:
-cell mediated immunity
-antibody mediated immunity

cell mediated immunity

-included specific and non-specific components
-3 cells involved; T-lymphocytes, natural killer cells and macrophages
-2 populations of lymphocytes derived from 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 the thymus gland, where they develop immunological competence

T-lymphocyte maturation

-T-lymphocytes have specific molecules on the cell surface, known as T-Cell Receptors (TCR), that recognise antigens
::antigens are only recognised by T-cells when ‘presented’ in the context of an MHC molecule::

-during maturation, any T-cell with a receptor that recognises self-antigens is destroyed
-therefore, mature T-cells only recognise foreign antigens
-mature T-cells are stored in an inactive state as “small lymphocytes”

T-cell activation

Foreign antigen is phagocytosed by 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 that 1 in 10,000 cells may respond

Antigen Presenting Cells

APC ingests and destroys the Antigen; fragments are ‘linked’ with MHC molecules (MHC complex) and expressed on the cell membrane of the APC cell

T-cell activation

the responding cell now becomes activated or sensitized the sensitized cell increases in size and divides mitotically to form a clone of cells similar to itself; the cells differentiate into a variety of specialised cells called T-cell subsets; there are at least 4 cell types: cytotoxic T-cells, helper T-cells, suppressor T-cells, memory cells; 1.The T-cells now 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) 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)

T-Lymphocyte Activation

Antigen presenting cell A competent T cell is activated by specific foreign antigen-MHC complex presented by an APC Helper T cells recognize a different foreign antigen-MHC complex and secrete cytokinesis that activate T cells activated T cells increase in size and divides by mitosis clone of competent T cells is produced

T-Lymphocyte Activation

T cells differentiate becoming various types of T cells T cells leave the lymph node and migrate to the site of infection cytotoxic t cells release proteins that destroy infected cells helper T cells release substances that attract macrophages and make other lymphocytes competent to help

T-Lymphocytes - T cell subsets (Cytotoxic T-lymphocytes)

recognise and destroy cells with foreign antigens including infected body cells (viruses), bacteria, protozoa, fungi, cancer cells, organ transplants

T-Lymphocytes : T cell subsets (Helper T-lymphocytes)

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

T-Lymphocytes - T cell subsets (Suppressor T-lymphocytes)

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

T-Lymphocytes - T cell subsets (Memory cells)

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

Natural killer cells

similar to cytotoxic T-cells, but non-specific, i.e. they do not depend on recognising and binding to foreign antigen instead, they recognise cells with altered cell-surface NK cell attack cancer cell Cancer cells often have unusual protein expression and their cell surface is abnormal – such cells are recognised and destroyed by NK cells

Immune Response

The first exposure of the body to a new pathogen elicits a primary immune response; the primary response may take from 3 to 14 days; subsequent exposure to the antigen will usually cause a more rapid and dramatic reaction called a secondary immune response the rapid response is due to the presence of memory cells bearing receptors to the antigen not only is the latent period shorter, much less antigen is required, more antibodies are produced and the pathogen is destroyed before it can get established this is why we do not usually get diseases such as measles and chickenpox more than once; unfortunately cold and influenza viruses continually mutate changing their surface antigens

Primary and secondary responses

The body is capable of mounting a specific response against a very large number of different antigens, (most of which it may never encounter) it takes a lot of resources to make specific T-cells, antibodies etc. The first encounter of a foreign antigen tells the body that particular antigen is in the environment, and that it is worthwhile to use up resources to combat it. memory cells are generated and the body is prepared for the next attack