Week 1 (Fundamentals and Immunization)

What is the basis of an immune response and what can failure of the immune system lead to?

immune response: the ability of the immune system to recognize self vs non-self (foreign substances)

failure → autoimmune diseases, allergy, cancer, alloimmunization

What is the definition of immunohematology?

the study of RBC antigens and their corresponding Abs. This includes other blood cells too and their corresponding Abs

What is the difference between innate and adaptive immunity?

innate: resisting infections by normal body functions

adaptive: host adapts to kill immunogen through complex recognition process (humoral and celullar)

What is the definition of an immunogen?

a substance that triggers an immune response

What are the definitions of autoantigen, alloantigen, heteroantigen, and hapten?)

autoantigen: normal host protein that is recognized as an antigen

alloantigen: same species diff person (blood)

heteroantigen: diff species diff person

hapten: small Ag that doesn’t trigger an immune response unless in complex w/ larger protein

What is the definition of immunogenicity?

ability of the immunogen to stimulate an immune response

What are the 3 WBCs of the innate immune system and what are their functions?

neutrophil: 1st responders that perform phagocytosis

eosinophil: kills parasites and neutralizes basophils/mast cells

basophils: induce allergic reactions and stimulate B cells to produce IgE

What are the 3 tissue cells and what are their functions?

monocyte: phagocytosis and migrate to tissue to become macrophages

mast cells: enhances adaptive immune response, binds to IgE

dendritic cells: most potent phagocytes

What are the 3 WBCs of the adaptive immune system and their functions?

T lymphs (CD4 and CD8): produce cytokines

B lymphs: produce ABs

NK cells: kills viruses and cancer cells. also produces cytokines

What markers do T helper and T cytotoxic cells have?

T helper: CD4

T cytotoxic: CD8

What is opsonization and the 3 opsonins?

opsonization: when opsonins coat the pathogen to faciliate phagocytosis

3 opsonins: Abs, complement, acute phase reactants

What do PAMP and PRR stand for?

PAMP: pathogen associated molecular pattern

PRR: pathogen recognition receptors Des

Describe the process of antigen presentation

1. phagocyte eats the bacteria

2. bacteria antigen goes to surface of phagocyte

3. phagocyte presents antigen to T helper cell

4. T helper cell activated

What does the activation of a T helper cell do?

results in activation of B cells and proliferation of more T helper cells

What are the 2 types of major histocompatibility complex (MHC) and where are they found?

MHC I: found in most nucleated cells

MHC II: found in antigen presenting cells (APC) aka phagocytes that present antigen (neutrophils, monocytes/macrophages, dendritic cells)

What are the general differences between the cellular and humoral elements of the adaptive immune response?

cellular: T cells that either release cytokines to activate B cells or attack cells

humoral: B cells that produce antibodies

What is an immunoglobulin and what are its 4 roles?

definition: Abs produced by plasma cells with specificity to an antigen

roles: bind Ag, activate complement, facilitate phagocytosis, neutralize toxic substances

Describe the structure of an Ab (Ig)

2 heavy chains and light chains

constant region in bottom and variable region on top

Fab region consists of heavy/light chain

Fab: binds to Ag

Fc: site of complement fixation and binds to monocytes

What is the difference between isotype, allotype and idiotype of Abs?

isotype: IgM, A, D, G from different type of heavy chain

allotype: genetic variation in heavy chain

idiotype: variable region has diff Ab specificity

What are the 3 key characteristics of IgG? (Fc region, can cross?, can activate?)

Fc region of IgG can bind to monocyte, macrophages, and neutrophil receptors

It can cross the placenta

Can activate complement

What are the key characteristics of IgM? (response, can cross?, can activate?, phag/tox)

primary response Ab that has no memory cells

cannot cross placenta

only 1 molecule of IgM needed to activate complement

enhances phagocytosis and neutralizes toxins

What are the key characteristics of IgA? (where found, can cross?, can activate?, regulates/deficiency )

found in bodily fluids and is an anti-inflammatory agent

cannot cross placenta

does not activate complement

regulates igG and deficiency → anaphylactic shock due to anti-igA development

What is the complement system and its 3 primary roles?

complex group of circulating cell membrane proteins.

1. opsonization: C3b attached to antigen recognized by phagocytes

2. promotes assembly of MAC

3. participates in acute inflammatory response

What are the 3 complement activation pathways?

1. classical: Ab directed mechanism

2. lectin: recognition unit used by mannose binding lectin

3. alternative: mainly to stabilize C3 convertase

What is the common pathway for all?

cleavage of C3 to C3b and assembly of MAC

Describe the classical complement pathway

1. C1qrs is activated

2. C4 and C2 are cleaves into C4a,C4b,C2a,C2b → C4b2a complex

3. C4b2a cleaves C3 into C3a,C3b → C4b2a3b

4. C4b2a3b cleaves C5 into C5a,C5b → C5b combines with C6,C7,C8,C9 → C5b6789

5. yellow = recognition, blue = activation, red = MAC

What complex is known as C3 convertase? C5 convertase?

C4b2a, C4b2a3b

Describe the lectin pathway

1. Mannose binding lectin binds to bacterial cell wall to activate complement

2. No C1, starts pathway with C4b2a and follows same pathway afterwards like classical pathway

Describe the alternative pathway

1. Factor C3 is hydrolyzed by water → C3b, which binds to factor B and both attach to target cell surface

2. Factor D cleaves B → Ba and Bb. Bb + C3b→ C3bBb, which has C3 convertase activity and is stabilized by properdin

3. Follows the rest of classical pathway

4. unique to this pathway are properdin, Factor B and D

What are the 3 functions of interleukins?

1. inflammation and fever

2. initiation of acute phase reactants

3. activation/growth of B/T lymphs

What are the 2 roles of tumor necrosis factors (TNF)?

1. induce lysis of tumor cells

2. activates T cells

What are the 3 roles of transforming growth factors? (TGF)

1. anti-inflammatory

2. inhibit T/B cell proliferation

3. inhibit macrophages

What are the 5 roles of interferon?

1. activate NK cells

2. increase MHC class I expression

3. increases Ag presentation

4. activates macrophages

5. protects host from viruses

What is the role of colony stimulating growth factors (CSGF)?

stimulate proliferation/differentiation of hematopoietic stem cell

What is hypercytokinemia (cytokine storm) and what can it cause?

it is the overproduction/stimulation of cytokines → septic shock and death

What are acute phase reactants and when are they released?

they are proteins (CRP, haptoglobin, fibrinogen, etc) that bind to microorganisms to promote phagocytosis (opsonins) and are released by liver cells when there is an increased level of cytokines

What is the difference between immunity and immunization?

immunity: condition of being resistant to a disease

immunization: process by which immunity is acquired

What is the mechanism, advantage, and limitation of active immunity?

mechanism: activation of humoral/cell mediated response by exposure to an antigen

advantage: long term memory against antigen

limitation: delay in the initiation of immune response

What is the mechanism, advantage, and limitation of passive immunity?

mechanism: transfer of Ab from immunized host → non-immunized person

advantage: provides immediate protection to the recipient

limitation: only temporary immunity, no memory, and hypersensitivity can be developed

What are some examples of passive immunity?

1. maternal IgG to fetus via placenta

2. maternal IgA to infant via breast milk

3. Rhogam

4. monoclonal Abs

5. human serum globulins

What is the mechanism, advantage, and limitation of the adoptive immunity?

mechanism: transfer of immune system cells to non-immune person

advantage: can transfer cell-mediated immunity

limitation: patient’s own cells must be depleted and allogeneic cells may be rejected

What is the composition of attenuated, inactivated, and subunit vaccines?

attenuated: live pathogens weakened by growth under modified culture conditions

inactivated: killed microorganisms

subunit: derived from 1 or more components of the pathogen

What are the 3 adverse effects of vaccines?

1. local inflammatory response @ site of injection

2. systemic inflammatory reactions (fever, nausea, etc.)

3. hypersensitivity reactions

What is the antigenic variation that allows a pathogen to escape immunity?

antigenic drift and shift

What are 3 scenarios of a failure in the host defense mechanism?

1. some viruses persist in vivo and stop replicating until immunity drops

2. some pathogens resist destruction and use host to survive

3. pathogens can cause immunosuppression