Immune disorders Flashcards

1
Q

Define the immune system?

A

A collection of mechanisms that protect against disease by identifying and killing pathogens, and tumour cells, and protection against microbial toxins.

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2
Q

What are the two major components of the immune system?

A
  1. Innate immunity
  2. Adaptive immunity (acquired)
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3
Q

Describe the innate immunity

A

Does not require prior exposure to a microbe to mount an immune response - it is always present and ready to attack.
-Born with, not specific
-Exposure leads to immediate maximal response
-Found in nearly all forms of life
-Phagocytes, NK cells, complement system

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4
Q

Describe the adaptive immunity

A

A more advanced system requiring exposure to an antigen in order to become active against microbes which have evaded the innate system
-Stronger immune response
-Specific and requires previous exposure to a stimulant
-Lag time between exposure and maximal response
-Cell mediated and humoral (antibody components)
-Exposure leads to immunological memory
-Found only in jawed vertebrates
-Highly malleable system due to somatic hypermutation and VDJ recombination of antigen receptor genes. Allows a small number of genes to generate an enormous number of antigen receptors that are uniquely expressed on each individual lymphocyte.
-Major components: lymphocytes (B cells and T cells), antigen presenting cells (dendritic cells, macrophages), human major histocompatibility complex (MHC) and complement system

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5
Q

Define immunology

A

The science that examines the structure and function of the immune system

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6
Q

Describe pathogens

A

Viruses, bacteria, mycobacteria, parasites and fungi

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7
Q

What are the general characteristics of immunity? (5)

A
  1. Recognition: the ability to distinguish between normal self, altered (damaged) self and non-self (foreign material)
  2. Specificity: the ability to inactivate, destroy and remove the “offending” material, without damaging normal tissues in the vicinity of the reaction, i.e. the reaction must be target-specific
  3. Regulation: the immune system is able to control the type, intensity and duration of the reaction and has the ability to prevent immune reaction (suppression)
  4. Amplification: the effector (attack) phase of the immune reaction is mediated through multiple pathways which act synergistically for optimal effect.
  5. Memory: the identity of the foreign material (antigen) which led to the first (primary) immune response is remembered so that the next episode involving the same antigen will result in an accelerated reaction (secondary immune response), which by-pass several initial steps that the primary immune response has to go through (confers long-term immunity).
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8
Q

What are natural killer cells?

A

-Recognized and destroy virus-infected cells as well as other damaged cells and tumour cells
-Recognize self via MHC class I molecules (expressed on all healthy cells)
-Damaged cells/tumour cells may not express normal MHC I, and NK cells will destroy them
-Damaged or stressed cells may bind to activating receptors on NK cells
-Express inhibitory and activating receptors. The receptor for MHC class I is an inhibitory receptor.
-They have innate ability to lyse viral infected cells and tumour cells without previous sensitization
-Produce the cytokine interferon in order to activate - interferon promotes their killing activity
-10-15% of peripheral cells; do not bear T-cell receptors or cell surface immunoglobulins
- Ability to lyse IgG-coated target cells (antibody-dependent cell-mediated cytotoxicity, ADCC)
- Have Cd16 and Cd56 surface molecules
- Prostaglanding E2 is highly suppressive of NK cells

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9
Q

What are the components of the innate immunity?

A
  1. Surface barriers - mechanical (skin), chemical (enzymes in saliva, vaginal secretions, tears), biological (bacterial flora)
  2. Humoral and chemical barriers - inflammation (one of first responses, produced as a result of: cytokines (e.g. interleukins), prostaglandins, leukotrienes, chemokines and interferons)
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10
Q

What are the cellular components of inflammation?

A
  • Neutrophils: phagocyte and release enzymes
  • Eosinophils and basophils: secrete chemical mediators
  • Monocytes/ macrophages: attack pathogens by engulfing and then killing the microorganisms by enzymes present within “lysosomes”
  • Mast cells: regulate the inflammatory response
    -Dendritic cells: phagocyte
  • Natural killer cells
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11
Q

Describe the complement system

A

It consists of more than 20 proteins and named as such due to its ability to “complement” the killing of a pathogen. They are synthesized mainly in the liver and normally circulate in the blood (plasma) in an inactive form.
-Recognize components of microbes (endotoxin, mannose residues) and are activated.

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12
Q

What can complement proteins be activated by?

A
  • Proteases (damaged cells, bacterial endotoxins) - proteolysis activates
  • Binding of the complement to antibodies that are attached to microbes
  • Binding complements carbohydrates on the microbes’ surfaces
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13
Q

What does complement activation result in?

A

-May form complexes with other complement proteins to kill microbes by direct cell lysis (membrane attack complex)
-Cell membrane disruption (lysis of target cell)
-Opsonization (coat) an organism, marking it for destruction
-Attraction of other immune cells through the production of peptides
-Release of various factors e.g. anaphylatoxins and chemotactic factors which result in acute inflammation
-Can also trigger the coagulation system, kinin system and fibrinolytic system
*May act as inflammatory mediators to recruit leukocytes, or may act as opsonins (C3b), coating microbes to target them for phagocytosis.

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14
Q

What are the two main types of adaptive immunity?

A
  • Humoral immunity
  • Cell mediated immunity
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15
Q

Describe humoral immunity

A
  • Antibody (immunoglobulin) - mediate, targets extracellular microbes
  • Antibodies are produced by plasma cells and are specifically directed against a particular antigen
  • Antibodies can neutralize microbes, promote their phagocytosis and destruction, and activate the complement system
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16
Q

Describe cell mediated immunity

A

Reaction of T-cells to attack cell-associated microbes

17
Q

What are antigen presenting cells (APCs)

A
  • Dendritic cells
  • Macrophages
  • B-cells
18
Q

Describe T-lymphocytes

A

Originate from primitive stem cells (yolk sac in embryos and bone marrow after birth), and mature in the thymus gland and differentiate into:
-helper/inducer cells (CD4), help other cell types to defend, B-cells, macrophages
- Suppressor/cytotoxic cells (CD8), direct killing of infected cells
* Constitute 60-70% of peripheral blood lymphocytes
Each cell is programmed to recognize a specific cell-bound antigen by means of an antigen-specific T-cell receptor (TCR). TCRs are linked to a cluster of five polypeptide chains, called CD3 molecular complexes. CD3 molecules do not bind antigen but are involved in the transduction of signals into the T cell after it has bound the antigen.

19
Q

Once activated, what do helper T-cell produce?

A
  • IFN-y, stimulates B-cells to produce Ig and activates macrophages
  • IL-2, stimulates proliferation of T-cells
  • Utilize CD40 ligand to stimulate macrophages to produce microbicidal substances and to activate B-cells
20
Q

Describe B-lymphocytes

A

Arise from yolk sac in embryos, and bone marrow after birth. Reach full maturation in the bone marrow, and migrate into peripheral blood and lymphoid tissue.
- Constitute 10-20% of peripheral lymphocytes
- Immature B-cells (pre-B) contain cytoplasmic heavy-chain immunoglobulins (Ig). Later they develop surface immunoglobulins (Ig).
- Mature B-cells are primarily in a resting, awaiting activation by foreign antigens. On antigenic stimulation, they form plasma cells which secrete 5 classes of immunoglobulins (M, G, A, D, and E)
- Recognize antigen via B-cell antigen receptor complex which includes a specific Ig. Major one is IgM antigen receptor complex. Other receptors are complement receptors, IgA and IgE, Cd40 and Fc receptors.
- T-cells and other nonspecific factors are required for maturation and differentiation of B-lymphocytes
- T-cells activate B-cells via CD40 (induces isotope switching of antibody class to allow a diversity of antibody function - promotes affinity maturation, production of antibodies with greater affinity for an antigen)
- B-cells also display peptides via MHC II for T-cell recognition

21
Q

What are macrophages?

A

Phagocytic cells, present virtually in all body organs. They are required to:
- Process and present antigens to immunocompetent T-cells
- Important in certain cell-mediated immunity such as delayed hypersensitivity reaction
- Important in the effector phase of humoral immunity (phagocytose opsonized microbes)
- They secrete macrophages-derived cytokines that amplify T-cell responses
- Display peptides via MHC II for T-cell recognition

22
Q

What are Dendritic cells?

A

Antigen presenting cells
- Phagocytic cells, but “preserve” antigens for potential presentation
- Have cytoplasmic processes with which to capture antigens
- Interdigitating dendritic cells express high levels of MHC antigens
- Follicular dendritic cells, bear Fc receptors for IgG

23
Q

What is the human major histocompatibility complex?

A

MHC is an intricate system of membrane proteins or antigens, from the human leukocyte antigens (HLA). MHC genes are located on chromosome 6 and code for three major classes of molecules (I, II, and III).
Extracellular portion binds antigen for presentation to T-cells (I and II).

24
Q

Describe the three types of MHC molecules:

A

I: present on all nucleated cells and recognized by cytotoxic T-cells (and NK cells), mostly bind peptide antigen derived from intracellular proteins (viral antigens) for display to cytotoxic cells
II: expressed on antigen-presenting cells (APCs) and B-cells for display to helper T-cells. Mostly bind peptide antigens derived from extracellular bacteria. Subsets of activated T cells.
III: a complement antigen and not a histocompatibility antigen - not part of peptide display system.