Module 3: Topic 2: Inappropriate Immune Responses Flashcards
What is an inappropriate immune response?
- Autoimmunity
- Alloimmunity
- Allergy
- Immune Deficiency
What is autoimmunity?
Misdirected responses against the host’s own tissues
What is alloimmunity?
(aka isoimmunity)
Directed responses against beneficial foreign tissues, such as transfusions or transplants
What is an allergy?
Exaggerated responses against environmental antigens
What is an immune deficiency?
Insufficient responses to protect the host.
What are inappropriate immune responses also known as?
Hypersensitivity reactions.
Briefly list and describe types of hypersnsitivity:
- Type I → IgE mediated allergic reaction
- Type II → Tissue specific reaction
- Type II → Immune complex-mediated reaction
- Type IV → Cell medieated
- Rarely associated w/ single disease
List examples of Type I hypersensitivities:
Anaphylaxis
Rhinitis
Urticaria
Eczema (Atopic Dermatitis)
Are hypersensitivity reactions immediate or delayed?
Both
Immediate: developing within minutes to a few hours
Delayed: developing within several hours or days
Discuss Type I hypersensitivities
- Type I (IgE-mediated)
- Occur within minutes of exposure
- Reactions are mediated through the binding of IgE to Fc receptors on mast cells and cross-linking of IgE by antigens that bind to the Fab portions of IgE.
- Cross- linking causes mast cell degranulation and the release of histamine (the most potent mediator) and other inflammatory substances.
Atopic Individual
Individuals that are genetically predisposed to develop allergies, particularly type I allergies.
Atopic individuals tend to produce higher quantities of
IgE and to have more Fc receptors for IgE on their mast cells.
The airways and the skin of atopic individuals are also more
responsive to a wide variety of both specific and nonspecific
stimuli than are the airways and skin of individuals who are
not atopic.
Describe Type I hypersensitivity process
Exposure to antigen
- Production of IgE
- Initiate degranulation of mast cells
- Histamine enhances the chemotaxis of eosinophils into sites of type I allergic reactions.
- Histamine 1 receptors (pro-inflammatory) cause vasodilation, bronchoconstriction, increased permeability
- Histamine 2 receptors (anti-inflammatory) increase gastric secretion and decrease release of histamine from mast cells and basophils
- Primary control of process in autonomic nervous system mediators
- Atopic individuals tend to produce higher quantities of IgE and to have more Fc receptors for IgE on their mast cells
Type I Mediators
Complement
- release of histamine, inflammatory response, leukocytosis, secondary release of cytokines
Acetylcholine
- bronchial smooth muscle contraction, dilation of small blood vessels
Slow-reacting substances of anaphylaxis
- Leukotrienes, prostaglandins (same as histamine & acetylcholine
Kinins
- require enzymatic activation
- vasodilatation, smooth muscle contraction, leukocyte chemotaxis, vascular permeability
Eosinophil chemotactic factor
- peptides released from mast cells & basophils after binding of surface IgE to allergen
- Chemotaxis of leukocytes & eosinophils
Clinical signs of Type I hypersensitivity
- GI: vomiting, diarrhea, abdominal pain {milk allergy}
- Skin: urticaria or hives, conjunctivitis, flushing, pruritus
- Respiratory: rhinitis, asthma, obstruction of lumen, edema, increased secretions, hyperplasia.
What is RIST?
Radio-immuno-sorvent Test
Tests circulating levels of IgE
What is RAST?
Radio-allergo-sorbent Test
Tests for circulating levels of antigen-specific IgE antibodies
Which is more specific: RIST or RAST?
RAST - checks for circulating levels of antigen-specific IgE antibodies.
What is desensitization?
Method to induce production of blocking antibody.
List common Type I hypersensitivities manifestations/diseases
- Allergic Rhinitis
- Food allergies - 90% egg, peanut, milk, fish, soy and wheat
Describe Type II Hypersensitivities
Type II (tissue-specific) reactions are caused by five possible mechanisms:
- complement- mediated lysis (example: hemolytic anemia)
- opsonization and phagocytosis; (example: RBCs in Rh system)
- neutrophil-mediated tissue damage;
- antibody- dependent, cell-mediated cytotoxicity;
- Does not destroy by causes cells to malfunction
- Example: ¡Graves disease antibody activated receptors on cytotoxic cells which are not antigen specific stimulate T4 production despite decrease in TSH
- and modulation of cellular function.
Some Drugs: drug binds to RBC or WBC with ADCC and cell lysis
What type of hypersensitivity is hemolytic anemia?
Type II (tissue-specific) reactions:
Complement- mediated lysis (example: hemolytic anemia)
What type of hypersensitivity reaction occurs in RBCs/Rh system?
Type II (tissue-specific) reactions
opsonization and phagocytosis; (example: RBCs in Rh system)
What type of hypersensitivity occurs in Grave’s disease?
Type II (tissue-specific) reactions are caused by five possible mechanisms:
Antibody- dependent, cell-mediated cytotoxicity:
- Does not destroy by causes cells to malfunction
- Example: Graves disease antibody activated receptors on cytotoxic cells which are not antigen specific stimulate T4 production despite a decrease in TSH and modulation of cellular function.
Some Drugs: drug binds to RBC or WBC with ADCC and cell lysis
Describe Type III Hypersensitivities
Type III (immune complex–mediated) reactions are caused by the formation of immune complexes that are deposited in target tissues.
They activate the complement cascade, generating chemotactic fragments that attract neutrophils into the inflammatory site.
Neutrophils release lysosomal enzymes that result in tissue damage.
Intermediate-sized immune complexes are the most likely to have severe pathologic consequences.
Immune complex disease can be a systemic reaction, such as serum sickness, or a localized response, such as the Arthus reaction.
What is serum sickness?
Related to Type II - Immune Complex Mediated injury:
- Deposits of immune complexes present in blood vessels, kidneys, joints
- Signs: fever, rash, pain, lymphadenopathy
- Decreased lymphocyte, granulocyte & platelet
What is the Raynaud phenomenon?
- Type III - Immune Complex mediated injury
- temperature dependent
- deposition of immune complexes in peripheral circulation
What is Arthus reaction?
- Type III Immune Complex Mediated injury
- Localized
- IgG localized on walls of blood vessels causing increased:
- neutrophils,
- edema,
- hemorrhage,
- clotting,
- tissue damage
Describe system classic pathway
- Activated @ C1 by AgAb complex
- C1-C5 – enhances inflammation & induces rapid mast cell degranulation affecting the respiratory system.
- C3a-C5a – anaphylatoxins are released, but may be inactivated by naturally occurring plasma enzymes
Describe effects of C1-C5 in the complement system classic pathway:
Enhances inflammation & induces rapid mast cell degranulation affecting the respiratory system.
Describe actions of C3a-C5a in the complement system classic pathway:
Anaphylatoxins are released but may be inactivated by naturally occurring plasma enzymes.
Describe characteristics of complement system alternate pathway:
- Activated @ C3b – provides bacterial opsonization.
- Non-AgAb mediated.
- Can adhere to membranes of polysaccharide bacteria & fungus; esp. Gm (-) endotoxins.
Describe Type IV Hypersensitivities
- Type IV (cell-mediated) reactions are caused by either cytotoxic T lymphocytes (Tc cells) or lymphokine-producing Th1 cells.
- Do not involve antibodies
- Clinical examples of type IV hypersensitivity reactions
include:- graft rejection
- allergic reactions resulting from contact with such substances as poison ivy and metals.
- A type IV component also may be present in many autoimmune diseases.
- T cells against type II collagen (a protein
present in joint tissues) contribute to the destruction of joints in rheumatoid arthritis; - T cells against a thyroid cell surface antigen contribute to the destruction of the thyroid in autoimmune
thyroiditis (Hashimoto disease); - and T cells against an antigen on the surface of pancreatic beta cells (the cell that normally
produces insulin) are responsible for beta-cell destruction in insulin-dependent (type 1) diabetes mellitus.
- T cells against type II collagen (a protein
Where in the body are Type IV hypersensitivities most common in the body?
The allergens that induce a type IV allergic reaction are mostly haptens that react with normal self-proteins in the skin.
The primary result is an allergic contact dermatitis that is confined to the area of contact with the allergen. The best-known example is poison ivy.
What is the difference between atopic vs. cell-mediated dermatitis?
As noted, type I hypersensitivity reactions may result in a skin reaction (e.g., hives formed during an allergic reaction to a particular food).
The distribution of the lesions may suggest whether the reaction is caused by immediate (type I) or delayed (type IV) hypersensitivity mechanisms.
Immediate hypersensitivity reactions, termed atopic dermatitis, are usually characterized by widely distributed lesions, whereas contact dermatitis (delayed hypersensitivity) consists of lesions only at the site of contact with the allergen, such as a metal allergy to jewelry.
Describe atopic dermatitis:
Immediate hypersensitivity reactions (type I), are usually characterized by widely distributed lesions.
Describe contact dermatitis:
Type IV hypersensitivity (cell-mediated)
(delayed hypersensitivity) consists of lesions only at the site of contact with the allergen, such as a metal allergy to jewelry.
Normal vs. Disease Associated Autoimmune Disorders
- To be able to recognize the universe of antigens, T and B cell receptors are randomly generated.
- The consequence of this is that lymphocytes
- with reactivity to self-antigens are also produced.
- To allow the host to survive those T or B cells must be eliminated or held in check
Type of immunity seen in transplant rejection:
Alloimmunity
Type of immunity seen in transient neonatal deiseases:
- Alloimmune disorder
- the maternal immune system becomes sensitized against antigens expressed by the fetus;
What is autoimmunity?
- A breakdown of immunologic homeostasis, the immune system’s tolerance of self-antigens.
- Lymphocytes cannot distinguish self from non-self
When is central tolerance developed?
During the embryonic period.
How is peripheral tolerance maintained?
In secondary lymphoid organs by regulatory T lymphocytes or antigen-presenting dendritic cells.
What type of immunity is present with transplant rejection and blood transfusion reactions?
Alloimmunity
T vs B Cell deficiencies - how to tell them apart:
Deficiencies in T-cell immune responses:
- certain viruses (e.g., varicella, vaccinia, herpes, cytomegalovirus),
- fungi and yeasts (e.g., Candida, Histoplasma), or
- certain atypical microorganisms (e.g., P. jirovecii).
B-cell deficiencies
- if recurrent infections with microorganisms that require opsonization (e.g., encapsulated bacteria) or
- viruses against which humoral immunity is normally effective (e.g., rubella).
Hallmark of T-cell immune deficiencies:
Deficiencies in T-cell immune responses:
- certain viruses (e.g., varicella, vaccinia, herpes, cytomegalovirus),
- fungi and yeasts (e.g., Candida, Histoplasma), or
- certain atypical microorganisms (e.g., P. jirovecii).
Hallmark of B-cell immune deficiencies
B-cell deficiencies
- if recurrent infections with microorganisms that require opsonization (e.g., encapsulated bacteria) or
- viruses against which humoral immunity is normally effective (e.g., rubella).
What is the clinical hallmark of immune deficiency?
The tendency to develop unusual or recurrent severe infections.
Should an immunocompromised person receive live virus vaccine?
NO! They may develop an uncontrolled infection.
Interventions for the Immunosuppressed
- Don’t give live attenuated virus – in particular OPV, varicella (not studied)
- May give IPV-e (enhanced inactivated polio virus)
- Do not give live virus to household members too
- All others including MMR OK
- Post-exposure passive immunization on case-by-case basis.
- May have blunted immune response to vaccine, so immunize early in disease course
Classic HIV infection manifestation
- Decreased CD4+ cells
- Frequent rampant infections unchecked by immune system
