Foundational Concepts- Abnormal Immune Response Flashcards
3 types of Abnormal Immune response
1) Immunodeficiency
2) Hypersensitivity
3) Autoimmunity
Define Immunodeficiency and difference between 1* and 2*
Partial or complete l/o Immune Response, leads to a predisposition to disease.
1* Primary- Genetic or Congenital. Developing failure (ex. Thymus)
2* Secondary- Acquired (post Natal) Possible causes:
• Immunosuppressive drugs (steroids)
• CA tx drugs
• Infection (ex. HIV) that affects organs of immune response
(Note: 2 kinds of immunity- Cell mediated (Humeral) or Antibody mediated)
5 types of immunodeficiency
• T-cell disorder -> Impaired T cell function
impairs the ability to orchestrate the immune responses (CD4 helper T cells) to protect against fungal, protozoan, viral and intracellular infections, at an inc risk for certain types of cancers.)
- B Cell Disorder -> impaired the ability to produce antibodies and defend against microorganisms and toxins that circulate in the body fluids IgM and IgG, prone to pyogenic infections.)
- T & B cell disorder (mix)
• Complement Disorders
of complement or the absence of a particular complement component can lead to enhanced susceptibility to infectious diseases and immune- mediated disorders such as hemolytic anemia and collagen vascular disorders.)
• Disorders of Phagocytosis
(A defect would leave a person prone to infections by bacteria)
Common Tx for Immunodeficiency
- Replacement therapy (Gamma Globulins) Synthetic antibodies
* Marrow/thymus transplant? (limited suucess)
Define Hypersensitivity and state 4 Types (ACID)
Type 1-3 B cell Related
HS-(Inappropriate/exaggerated/hyper IR (causes inflm and all inflm causes some tissue damage)
• Type 1- IgE mediated hypersensitivity or Allergy
• Type 2- Cytotoxic Hypersensitivity (or tissue specific H)
• Type 3- Immune complex H
• Type 4- T-cell mediated H (or Delayed H)
Define Type 1 HS + Steps of progression
Fig 9-3- Allergy
• Most common, IgE (antibody) mediated
• D/t allergies (drugs or food)
• Rapid Response
Progression
Sensitization (on first expose only)
• Ag -> T Helper -> B- cell stimulation -> Ab IgE forms -> attaches to Mast cell – Mast cell is now “sensitized” to Ag
• ANY SUBSEQUENT EXPOSURE
Ag (Binds) -> Mast cell (degranulation and mediator release) -> INFLM. Target area becomes red, swollen and pruritic
Ex. Allergy, Type 1 H is a part of Asthma, Anaphylaxis (life threatening and severe allergy)
Tell me about septic shock
(Not type 1 HS)
• D/t severe infection (not allergic reaction)
• Based on the traditional inflammation response but infection has reached such a level that mediators are released at a systemic level (or at least a whole organ system) the result is mass vasodialation and resulting systemic hypotension
Kind of distributive shock
Tell me about Anaphylactic shock
• Severe allergic Rx
• Type 1 HS Rx -> mediator release -> Excessive vasodilation
• No localized injury necessarily, large scale systemic mediator release by mast cells
o Excessive vasodialation and increase in Cap permeability
o Fluid loss into interstitial space from blood vessel- i.e edema (this can occur in resp. tract)
o Mediators released act on smooth muscle on airway (bronchospasm) locked in constrictive state (Note: spasm here is not traditional muscle spasm, but a locked position)
Define Type ll HS- Progression and Key Mediatos
Cytotoxic Mediated HS
• AB mediated (IgM and IgG specifically) Miss target self-antigens
• Ab + Ag -> Immune complex where Ag bearing cell is destroyed by: Complement, phagocytosis, inflm
o When personal cells are destroyed there is damage to tissue = INLFM
FIG 19-5
What happens in a incompatible blood transfusion
o Person has A blood and has B Ab, you give them B blood with A Ab they attack each other.
o Although there is overlap this is not auto immunity
Define Type lll HS- Progression and Key Mediators
Immune Complex Hypersensitivity
• I. C. (immune Complex) not broken down ( Why? could be very small and avoid detection or water insoluble and hard to breakdown)
• Normally Ag + Ab -> I. C. and complete enzyme breakdown of I.C. immediately afterward
• Result (Fig 19-5) of excess I. C. is their deposition in constriction of the CV system (i.e. capillaries and endothelium) Causes problems
1) Block pores and effect transcapillary exchange
2) When cleared away by macrophages can create holes and tissue damage along endothelium
Ex. Glomerulonephritis and rheumatoid arthritis (part is type 3 HS)
Type 4 HS
Delayed HS T-cell Hypersensitivity (19-6)
• Not Ab mediated
• Normal response: Non-specific defense (macrophages) ingest, destroy, and presents chewed up Ag to T helper to begin production of T cytotoxic.
• Some self cells have Ag leftovers and are destroyed (i.e. tissue damage and INFLM). T cell targets macrophage as well.
• Macrophage -> presents Ag to T helper -> T cell sensitized ->cytotoxic T cell created -> destruction of Ag bearing cell -> inflm and damage
2 types –
• Direct (stat) directly destroying Ag bearing cells
• Delayed- production of lymphokynes (chem mediators) to destroy Ag (days)
Review- What is an Antigen
Antigens (Ag) are any structural substance that serves as a target for adaptive immune response. Specifically proteins on cells that fx as markers of the cell. Self cells are normally tolerated while foreign cells destroyed through immune response.
Define Autoimmunity
Autoimmunity is the system of immune responses of an organism against its own cells and tissues. Loss of “self –tolerance” self-cells can be considered foreign cells. Antibodies then target self antigens causing inflm damage and necrosis
NOTES
• Autoimmune diseases are generally continuous not episodic. Can be some overlap between autoimmune and HS
• MHC/HLA are the protein complex’s that generally identifIES the antigen and cell
Autoimmunity- 3 ways self tolerance can be lost
1) Abnormal T-cell activity
2) Molecular Mimicry
3) Exposure of previously masked self-antigen
Autoimmunity- Discuss Abnormal T cell Activity
A type of l/o self tolerance
Normally T suppressor cells suppress action of cytotoxic T cells after foreign antigen has been destroyed. The abnormal action is the cytotoxic T cell continue fx without the presence of the antigen and become “bored” while continuing to float around. T cells continue to release enzymes now and again which break down other cells unrelated to original Ag.
Autoimmunity- Discuss Molecular mimicry
A type of l/o self tolerance
o Similar epitope causes cell to be identified as foreign (i.e. the component of antigen that antibody recognizes and binds to.
Notes:
Epitope is a protein or part of protein. Changes in the amino acid sequence is what changes the protein characteristic, a similar amino acid sequence may cause a cell to be misabeled and targeted)
Autoimmunity- Discuss Previously Masked self-antigen
A type of l/o self tolerance
Masked meaning not exposed to T cells/immune response. After development, some areas could remain closed to immune response, an injury or infection may bring out previously hidden Antigen that the Immune system may see as foreign (ocular disease)
oEx. SLE (lupus) targets nuclear component (all cells)
Would you like a very in depth explanation of type 1 hypersensitivity?
Is an IgE-mediated immune response that leads to the release of inflammatory mediators for sensitized mast cells. Some people develop an allergic reaction or hypersensitivity when exposed to substances such as dust, pollen, animal dander, or penicillin. This hypersensitivity is mediated by IgE. Sensitization occurs when the antigen makes contact with some part of the body. The Antigen is taken up, processed by antigen presenting cells, and presented on the class 2 MHC T helper cells (TH2). Tissues under the mucas membrane are rich in B cells, committed to IgE production, and IgE producing cells are more abundant in persons susceptible to allergies. The T helper cells produce a cytokines, which stimulate these B cells to proliferate and differentiate, to IgE presenting Plasma cells. As IgE produced in specific areas in the body, the IgE molecules attach via their constant reigns to receptors on the near by Mast cells. Mast cells containing graduals packed with chemicals that induce Hypersensitivity response. Once attached, the IgE molecule can survive for many weeks. The individual is now sensitized to the antigen.
When exposed to the antigen for the second time, the antigen binds to the IgE antibodies and the mast cells. Within seconds of reaction, the mast cell releases histamine and other mediators of the inflammatory response from the graduals, triggering inflm causing a variety of symptoms: Capillary dilation, Airway constriction, Mucus secretion, Pain, Itching. (Teachers notes: red, swollen, prutitic (prutitis) = itching.
If you are unlucky, and allergic, the second exposure to something causes your body to overproduce IgE, which causes over release of histamine and other mediators. Causes swelling and airway constriction, therefore you can’t breath. Tx is Adrenaline, causes fight or flight, thus relaxes airways so you can breath better.
- allergen detected byTH2 stimulatesBcells to produceIGE which attach toMast cells∴the Mast cells are said to be sensitized
- re-exposureallergen to bind to IgE on mast
cellmediator releaseinflm
- target areasred, swollen, pruritic (pruritis) =
itching
